{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T06:09:49Z","timestamp":1793945389850,"version":"4.8.0"},"reference-count":376,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Rev Cancer"],"published-print":{"date-parts":[[2026,7]]},"DOI":"10.1038\/s41568-026-00929-9","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T16:01:48Z","timestamp":1776960108000},"page":"534-554","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Context-dependent synthetic lethality \u2014 an emerging precision therapeutic approach"],"prefix":"10.1038","volume":"26","author":[{"given":"Liang","family":"Chang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katharin","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3539-9803","authenticated-orcid":false,"given":"William R.","family":"Sellers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"929_CR1","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/nature03095","volume":"432","author":"C Sawyers","year":"2004","unstructured":"Sawyers, C. Targeted cancer therapy. Nature 432, 294\u2013297 (2004).","journal-title":"Nature"},{"key":"929_CR2","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1038\/nrc1529","volume":"5","author":"BA Chabner","year":"2005","unstructured":"Chabner, B. A. & Roberts, T. G. Jr. Timeline: chemotherapy and the war on cancer. Nat. Rev. Cancer 5, 65\u201372 (2005).","journal-title":"Nat. Rev. Cancer"},{"key":"929_CR3","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1038\/s41392-021-00572-w","volume":"6","author":"L Zhong","year":"2021","unstructured":"Zhong, L. et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal. Transduct. Target. Ther. 6, 201 (2021).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"929_CR4","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1056\/NEJM200104053441401","volume":"344","author":"BJ Druker","year":"2001","unstructured":"Druker, B. J. et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344, 1031\u20131037 (2001).","journal-title":"N. Engl. J. Med."},{"key":"929_CR5","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1056\/NEJMoa1609324","volume":"376","author":"A Hochhaus","year":"2017","unstructured":"Hochhaus, A. et al. Long-term outcomes of imatinib treatment for chronic myeloid leukemia. N. Engl. J. Med. 376, 917\u2013927 (2017).","journal-title":"N. Engl. J. Med."},{"key":"929_CR6","doi-asserted-by":"publisher","first-page":"2380","DOI":"10.1056\/NEJMoa0909530","volume":"362","author":"M Maemondo","year":"2010","unstructured":"Maemondo, M. et al. Gefitinib or chemotherapy for non-small-cell lung cancer with mutated EGFR. N. Engl. J. Med. 362, 2380\u20132388 (2010).","journal-title":"N. Engl. J. Med."},{"key":"929_CR7","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1016\/S1470-2045(11)70184-X","volume":"12","author":"C Zhou","year":"2011","unstructured":"Zhou, C. et al. Erlotinib versus chemotherapy as first-line treatment for patients with advanced EGFR mutation-positive non-small-cell lung cancer (OPTIMAL, CTONG-0802): a multicentre, open-label, randomised, phase 3 study. Lancet Oncol. 12, 735\u2013742 (2011).","journal-title":"Lancet Oncol."},{"key":"929_CR8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S1470-2045(11)70393-X","volume":"13","author":"R Rosell","year":"2012","unstructured":"Rosell, R. et al. Erlotinib versus standard chemotherapy as first-line treatment for European patients with advanced EGFR mutation-positive non-small-cell lung cancer (EURTAC): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 13, 239\u2013246 (2012).","journal-title":"Lancet Oncol."},{"key":"929_CR9","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1038\/nature12796","volume":"503","author":"JM Ostrem","year":"2013","unstructured":"Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A. & Shokat, K. M. K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions. Nature 503, 548\u2013551 (2013).","journal-title":"Nature"},{"key":"929_CR10","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1056\/NEJMoa2204619","volume":"387","author":"PA J\u00e4nne","year":"2022","unstructured":"J\u00e4nne, P. A. et al. Adagrasib in non-small-cell lung cancer harboring a KRASG12C mutation. N. Engl. J. Med. 387, 120\u2013131 (2022).","journal-title":"N. Engl. J. Med."},{"key":"929_CR11","doi-asserted-by":"publisher","first-page":"2371","DOI":"10.1056\/NEJMoa2103695","volume":"384","author":"F Skoulidis","year":"2021","unstructured":"Skoulidis, F. et al. Sotorasib for lung cancers with KRAS p.G12C mutation. N. Engl. J. Med. 384, 2371\u20132381 (2021).","journal-title":"N. Engl. J. Med."},{"key":"929_CR12","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1016\/j.ccell.2020.12.008","volume":"39","author":"L Chang","year":"2021","unstructured":"Chang, L., Ruiz, P., Ito, T. & Sellers, W. R. Targeting pan-essential genes in cancer: challenges and opportunities. Cancer Cell 39, 466\u2013479 (2021).","journal-title":"Cancer Cell"},{"key":"929_CR13","doi-asserted-by":"publisher","first-page":"818","DOI":"10.1158\/2159-8290.CD-17-0151","volume":"7","author":"AACR Project GENIE Consortium.","year":"2017","unstructured":"AACR Project GENIE Consortium. AACR project GENIE: powering precision medicine through an international consortium. Cancer Discov. 7, 818\u2013831 (2017).","journal-title":"Cancer Discov."},{"key":"929_CR14","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1038\/nature12634","volume":"502","author":"C Kandoth","year":"2013","unstructured":"Kandoth, C. et al. Mutational landscape and significance across 12 major cancer types. Nature 502, 333\u2013339 (2013).","journal-title":"Nature"},{"key":"929_CR15","doi-asserted-by":"publisher","first-page":"1113","DOI":"10.1038\/ng.2764","volume":"45","author":"The Cancer Genome Atlas Research Ne","year":"2013","unstructured":"The Cancer Genome Atlas Research Network. The Cancer Genome Atlas Pan-Cancer analysis project. Nat. Genet. 45, 1113\u20131120 (2013).","journal-title":"Nat. Genet."},{"key":"929_CR16","doi-asserted-by":"publisher","first-page":"941","DOI":"10.1038\/s10038-018-0481-4","volume":"63","author":"D Hsiehchen","year":"2018","unstructured":"Hsiehchen, D. & Hsieh, A. Nearing saturation of cancer driver gene discovery. J. Hum. Genet. 63, 941\u2013943 (2018).","journal-title":"J. Hum. Genet."},{"key":"929_CR17","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1093\/genetics\/59.1.37","volume":"59","author":"JC Lucchesi","year":"1968","unstructured":"Lucchesi, J. C. Synthetic lethality and semi-lethality among functionally related mutants of Drosophila melanogaster. Genetics 59, 37\u201344 (1968).","journal-title":"Genetics"},{"key":"929_CR18","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1126\/science.278.5340.1064","volume":"278","author":"LH Hartwell","year":"1997","unstructured":"Hartwell, L. H., Szankasi, P., Roberts, C. J., Murray, A. W. & Friend, S. H. Integrating genetic approaches into the discovery of anticancer drugs. Science 278, 1064\u20131068 (1997).","journal-title":"Science"},{"key":"929_CR19","first-page":"328","volume":"60","author":"JA Simon","year":"2000","unstructured":"Simon, J. A. et al. Differential toxicities of anticancer agents among DNA repair and checkpoint mutants of Saccharomyces cerevisiae. Cancer Res. 60, 328\u2013333 (2000).","journal-title":"Cancer Res."},{"key":"929_CR20","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1038\/nature03445","volume":"434","author":"H Farmer","year":"2005","unstructured":"Farmer, H. et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434, 917\u2013921 (2005).","journal-title":"Nature"},{"key":"929_CR21","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1016\/j.cell.2017.07.005","volume":"170","author":"ER McDonald 3rd","year":"2017","unstructured":"McDonald, E. R. 3rd et al. Project DRIVE: a compendium of cancer dependencies and synthetic lethal relationships uncovered by large-scale, deep RNAi screening. Cell 170, 577\u2013592 (2017).","journal-title":"Cell"},{"key":"929_CR22","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","volume":"170","author":"A Tsherniak","year":"2017","unstructured":"Tsherniak, A. et al. Defining a cancer dependency map. Cell 170, 564\u2013576 (2017).","journal-title":"Cell"},{"key":"929_CR23","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/s41586-019-1103-9","volume":"568","author":"FM Behan","year":"2019","unstructured":"Behan, F. M. et al. Prioritization of cancer therapeutic targets using CRISPR\u2013Cas9 screens. Nature 568, 511\u2013516 (2019).","journal-title":"Nature"},{"key":"929_CR24","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21870","author":"C Hage Chehade","year":"2025","unstructured":"Hage Chehade, C. et al. A pan-tumor review of the role of poly(adenosine diphosphate ribose) polymerase inhibitors. CA Cancer J. Clin. https:\/\/doi.org\/10.3322\/caac.21870 (2025).","journal-title":"CA Cancer J. Clin."},{"key":"929_CR25","doi-asserted-by":"publisher","first-page":"564","DOI":"10.1038\/s41571-018-0055-6","volume":"15","author":"A Ashworth","year":"2018","unstructured":"Ashworth, A. & Lord, C. J. Synthetic lethal therapies for cancer: what\u2019s next after PARP inhibitors? Nat. Rev. Clin. Oncol. 15, 564\u2013576 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"929_CR26","doi-asserted-by":"publisher","first-page":"2412","DOI":"10.1158\/2159-8290.CD-23-0669","volume":"13","author":"LD Engstrom","year":"2023","unstructured":"Engstrom, L. D. et al. MRTX1719 is an MTA-cooperative PRMT5 inhibitor that exhibits synthetic lethality in preclinical models and patients with MTAP-deleted cancer. Cancer Discov. 13, 2412\u20132431 (2023).","journal-title":"Cancer Discov."},{"key":"929_CR27","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1038\/nrg.2017.47","volume":"18","author":"NJ O\u2019Neil","year":"2017","unstructured":"O\u2019Neil, N. J., Bailey, M. L. & Hieter, P. Synthetic lethality and cancer. Nat. Rev. Genet. 18, 613\u2013623 (2017).","journal-title":"Nat. Rev. Genet."},{"key":"929_CR28","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1038\/s41573-019-0046-z","volume":"19","author":"A Huang","year":"2020","unstructured":"Huang, A., Garraway, L. A., Ashworth, A. & Weber, B. Synthetic lethality as an engine for cancer drug target discovery. Nat. Rev. Drug. Discov. 19, 23\u201338 (2020).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"929_CR29","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.cell.2018.03.035","volume":"173","author":"F Sanchez-Vega","year":"2018","unstructured":"Sanchez-Vega, F. et al. Oncogenic signaling pathways in the cancer genome atlas. Cell 173, 321\u2013337 (2018).","journal-title":"Cell"},{"key":"929_CR30","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1016\/j.ccell.2017.06.010","volume":"32","author":"M Mina","year":"2017","unstructured":"Mina, M. et al. Conditional selection of genomic alterations dictates cancer evolution and oncogenic dependencies. Cancer Cell 32, 155\u2013168 (2017).","journal-title":"Cancer Cell"},{"key":"929_CR31","doi-asserted-by":"publisher","first-page":"i284","DOI":"10.1093\/bioinformatics\/btv247","volume":"31","author":"Y-A Kim","year":"2015","unstructured":"Kim, Y.-A., Cho, D.-Y., Dao, P. & Przytycka, T. M. MEMCover: integrated analysis of mutual exclusivity and functional network reveals dysregulated pathways across multiple cancer types. Bioinformatics 31, i284\u2013i292 (2015).","journal-title":"Bioinformatics"},{"key":"929_CR32","doi-asserted-by":"publisher","first-page":"e06907","DOI":"10.7554\/eLife.06907","volume":"4","author":"AM Unni","year":"2015","unstructured":"Unni, A. M., Lockwood, W. W., Zejnullahu, K., Lee-Lin, S.-Q. & Varmus, H. Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma. eLife 4, e06907 (2015).","journal-title":"eLife"},{"key":"929_CR33","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1136\/gutjnl-2011-301839","volume":"61","author":"N Deng","year":"2012","unstructured":"Deng, N. et al. A comprehensive survey of genomic alterations in gastric cancer reveals systematic patterns of molecular exclusivity and co-occurrence among distinct therapeutic targets. Gut 61, 673\u2013684 (2012).","journal-title":"Gut"},{"key":"929_CR34","doi-asserted-by":"publisher","first-page":"1709","DOI":"10.1038\/s41588-023-01515-7","volume":"55","author":"L Chang","year":"2023","unstructured":"Chang, L. et al. Systematic profiling of conditional pathway activation identifies context-dependent synthetic lethalities. Nat. Genet. 55, 1709\u20131720 (2023).","journal-title":"Nat. Genet."},{"key":"929_CR35","doi-asserted-by":"publisher","first-page":"1613","DOI":"10.1038\/s41588-023-01493-w","volume":"55","author":"KC Wood","year":"2023","unstructured":"Wood, K. C. Hyperactivation of oncogenic driver pathways as a precision therapeutic strategy. Nat. Genet. 55, 1613\u20131614 (2023).","journal-title":"Nat. Genet."},{"key":"929_CR36","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1038\/ncponc0558","volume":"3","author":"IB Weinstein","year":"2006","unstructured":"Weinstein, I. B. & Joe, A. K. Mechanisms of disease: oncogene addiction\u2014a rationale for molecular targeting in cancer therapy. Nat. Clin. Pract. Oncol. 3, 448\u2013457 (2006).","journal-title":"Nat. Clin. Pract. Oncol."},{"key":"929_CR37","doi-asserted-by":"publisher","first-page":"3077","DOI":"10.1158\/0008-5472.CAN-07-3293","volume":"68","author":"IB Weinstein","year":"2008","unstructured":"Weinstein, I. B. & Joe, A. Oncogene addiction. Cancer Res. 68, 3077\u20133080 (2008). discussion 3080.","journal-title":"Cancer Res."},{"key":"929_CR38","doi-asserted-by":"publisher","first-page":"4618","DOI":"10.1158\/1078-0432.CCR-21-2138","volume":"28","author":"PI Poulikakos","year":"2022","unstructured":"Poulikakos, P. I., Sullivan, R. J. & Yaeger, R. Molecular pathways and mechanisms of BRAF in cancer therapy. Clin. Cancer Res. 28, 4618\u20134628 (2022).","journal-title":"Clin. Cancer Res."},{"key":"929_CR39","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1200\/JCO.2011.36.1196","volume":"30","author":"F Janku","year":"2012","unstructured":"Janku, F. et al. PI3K\/AKT\/mTOR inhibitors in patients with breast and gynecologic malignancies harboring PIK3CA mutations. J. Clin. Oncol. 30, 777\u2013782 (2012).","journal-title":"J. Clin. Oncol."},{"key":"929_CR40","doi-asserted-by":"publisher","first-page":"3095","DOI":"10.1200\/JCO.2023.41.16_suppl.3095","volume":"41","author":"MR Patel","year":"2023","unstructured":"Patel, M. R. et al. BLU-222, an oral, potent, and selective CDK2 inhibitor, in patients with advanced solid tumors: phase 1 monotherapy dose escalation. J. Clin. Oncol. 41, 3095\u20133095 (2023).","journal-title":"J. Clin. Oncol."},{"key":"929_CR41","doi-asserted-by":"publisher","first-page":"3010","DOI":"10.1200\/JCO.2023.41.16_suppl.3010","volume":"41","author":"TA Yap","year":"2023","unstructured":"Yap, T. A. et al. First-in-human phase 1\/2a study of a potent and novel CDK2-selective inhibitor PF-07104091 in patients (pts) with advanced solid tumors, enriched for CDK4\/6 inhibitor resistant HR+\/HER2\u2212 breast cancer. J. Clin. Oncol. 41, 3010\u20133010 (2023).","journal-title":"J. Clin. Oncol."},{"key":"929_CR42","doi-asserted-by":"publisher","first-page":"S495","DOI":"10.1016\/j.annonc.2024.08.684","volume":"35","author":"M Simonelli","year":"2024","unstructured":"Simonelli, M. et al. 617MO Safety and tolerability of INCB123667, a selective CDK2 inhibitor, in patients (pts) with advanced solid tumors: A phase I study. Ann. Oncol. 35, S495 (2024).","journal-title":"Ann. Oncol."},{"key":"929_CR43","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1158\/2159-8290.CD-23-0954","volume":"14","author":"C Dietrich","year":"2024","unstructured":"Dietrich, C. et al. INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. Cancer Discov. 14, 446\u2013467 (2024).","journal-title":"Cancer Discov."},{"key":"929_CR44","doi-asserted-by":"publisher","first-page":"5603","DOI":"10.1200\/JCO.2025.43.16_suppl.5603","volume":"43","author":"D Lorusso","year":"2025","unstructured":"Lorusso, D. et al. Interim safety and antitumor activity data from a phase 1 study of INCB123667, a selective CDK2 inhibitor, in patients with metastatic recurrent endometrial cancer. J. Clin. Oncol. 43, 5603\u20135603 (2025).","journal-title":"J. Clin. Oncol."},{"key":"929_CR45","doi-asserted-by":"crossref","unstructured":"Montero, A. J. et al. Abstract PS4-06-08: a phase 1\/2, first-in-human study of AVZO-021, a selective cyclin-dependent kinase 2 inhibitor (CDK2i), as a monotherapy and in combination for patients with advanced solid tumors, including hormone receptor-positive (HR+)\/human epidermal growth factor receptor 2-negative (HER2\u2212) breast cancer and cyclin E1 (CCNE1)-amplified solid tumors: preliminary safety and efficacy results. Clin. Cancer Res. 32, PS4-06-08-PS4-06\u201308 (2026).","DOI":"10.1158\/1557-3265.SABCS25-PS4-06-08"},{"key":"929_CR46","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1016\/j.celrep.2019.08.090","volume":"29","author":"R Sulahian","year":"2019","unstructured":"Sulahian, R. et al. Synthetic lethal interaction of SHOC2 depletion with MEK inhibition in RAS-driven cancers. Cell Rep. 29, 118\u2013134 (2019).","journal-title":"Cell Rep."},{"key":"929_CR47","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/s41586-022-05086-1","volume":"609","author":"ZJ Hauseman","year":"2022","unstructured":"Hauseman, Z. J. et al. Structure of the MRAS\u2013SHOC2\u2013PP1C phosphatase complex. Nature 609, 416\u2013423 (2022).","journal-title":"Nature"},{"key":"929_CR48","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1038\/s41586-022-04838-3","volume":"609","author":"NPD Liau","year":"2022","unstructured":"Liau, N. P. D. et al. Structural basis for SHOC2 modulation of RAS signalling. Nature 609, 400\u2013407 (2022).","journal-title":"Nature"},{"key":"929_CR49","doi-asserted-by":"publisher","first-page":"e41305","DOI":"10.7554\/eLife.41305","volume":"7","author":"GL Brien","year":"2018","unstructured":"Brien, G. L. et al. Targeted degradation of BRD9 reverses oncogenic gene expression in synovial sarcoma. eLife 7, e41305 (2018).","journal-title":"eLife"},{"key":"929_CR50","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09891-7","volume":"10","author":"X Wang","year":"2019","unstructured":"Wang, X. et al. BRD9 defines a SWI\/SNF sub-complex and constitutes a specific vulnerability in malignant rhabdoid tumors. Nat. Commun. 10, 1881 (2019).","journal-title":"Nat. Commun."},{"key":"929_CR51","doi-asserted-by":"publisher","first-page":"3020","DOI":"10.1200\/JCO.2023.41.16_suppl.3020","volume":"41","author":"AE Drilon","year":"2023","unstructured":"Drilon, A. E. et al. A first-in-human, phase 1 study of the SHP2 inhibitor PF-07284892 as monotherapy and in combination with different targeted therapies in oncogene-driven, treatment-resistant solid tumors. J. Clin. Oncol. 41, 3020\u20133020 (2023).","journal-title":"J. Clin. Oncol."},{"key":"929_CR52","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1200\/JCO.2021.39.15_suppl.3005","volume":"39","author":"I Brana","year":"2021","unstructured":"Brana, I. et al. Initial results from a dose finding study of TNO155, a SHP2 inhibitor, in adults with advanced solid tumors. J. Clin. Oncol. 39, 3005\u20133005 (2021).","journal-title":"J. Clin. Oncol."},{"key":"929_CR53","doi-asserted-by":"publisher","first-page":"7773","DOI":"10.1021\/acs.jmedchem.6b00680","volume":"59","author":"J Garcia Fortanet","year":"2016","unstructured":"Garcia Fortanet, J. et al. Allosteric inhibition of SHP2: identification of a potent, selective, and orally efficacious phosphatase inhibitor. J. Med. Chem. 59, 7773\u20137782 (2016).","journal-title":"J. Med. Chem."},{"key":"929_CR54","first-page":"S802","volume":"35","author":"J Wang","year":"2024","unstructured":"Wang, J. et al. Efficacy of glecirasib in combination with JAB-3312 as a front-line treatment for patients with KRAS p.G12C mutated NSCLC with PD-L1 expression levels of co-mutations. Ann. Clin. Oncol. 35, S802\u2013S887 (2024).","journal-title":"Ann. Clin. Oncol."},{"key":"929_CR55","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1016\/0092-8674(90)90409-8","volume":"63","author":"M Scheffner","year":"1990","unstructured":"Scheffner, M., Werness, B. A., Huibregtse, J. M., Levine, A. J. & Howley, P. M. The E6 oncoprotein encoded by human papillomavirus types 16 and 18 promotes the degradation of p53. Cell 63, 1129\u20131136 (1990).","journal-title":"Cell"},{"key":"929_CR56","doi-asserted-by":"publisher","first-page":"495","DOI":"10.1016\/0092-8674(93)90384-3","volume":"75","author":"M Scheffner","year":"1993","unstructured":"Scheffner, M., Huibregtse, J. M., Vierstra, R. D. & Howley, P. M. The HPV-16 E6 and E6-AP complex functions as a ubiquitin-protein ligase in the ubiquitination of p53. Cell 75, 495\u2013505 (1993).","journal-title":"Cell"},{"key":"929_CR57","doi-asserted-by":"publisher","first-page":"8797","DOI":"10.1073\/pnas.91.19.8797","volume":"91","author":"M Scheffner","year":"1994","unstructured":"Scheffner, M., Huibregtse, J. M. & Howley, P. M. Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53. Proc. Natl Acad. Sci. USA 91, 8797\u20138801 (1994).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR58","doi-asserted-by":"publisher","first-page":"6439","DOI":"10.1074\/jbc.273.11.6439","volume":"273","author":"AL Talis","year":"1998","unstructured":"Talis, A. L., Huibregtse, J. M. & Howley, P. M. The role of E6AP in the regulation of p53 protein levels in human papillomavirus (HPV)-positive and HPV-negative cells. J. Biol. Chem. 273, 6439\u20136445 (1998).","journal-title":"J. Biol. Chem."},{"key":"929_CR59","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.tig.2024.04.013","volume":"40","author":"A Schreuder","year":"2024","unstructured":"Schreuder, A., Wendel, T. J., Dorresteijn, C. G. V. & Noordermeer, S. M. (Single-stranded DNA) gaps in understanding BRCAness. Trends Genet. 40, 757\u2013771 (2024).","journal-title":"Trends Genet."},{"key":"929_CR60","doi-asserted-by":"publisher","first-page":"103847","DOI":"10.1016\/j.dnarep.2025.103847","volume":"150","author":"Z Xu","year":"2025","unstructured":"Xu, Z., Xie, H., Song, L., Huang, Y. & Huang, J. BRCA1 and BRCA2 in DNA damage and replication stress response: Insights into their functions, mechanisms, and implications for cancer treatment. DNA Repair. 150, 103847 (2025).","journal-title":"DNA Repair."},{"key":"929_CR61","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1016\/j.trecan.2024.06.008","volume":"10","author":"D Dibitetto","year":"2024","unstructured":"Dibitetto, D., Widmer, C. A. & Rottenberg, S. PARPi, BRCA, and gaps: controversies and future research. Trends Cancer 10, 857\u2013869 (2024).","journal-title":"Trends Cancer"},{"key":"929_CR62","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1038\/nrm.2017.53","volume":"18","author":"A Ray Chaudhuri","year":"2017","unstructured":"Ray Chaudhuri, A. & Nussenzweig, A. The multifaceted roles of PARP1 in DNA repair and chromatin remodelling. Nat. Rev. Mol. Cell Biol. 18, 610\u2013621 (2017).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"929_CR63","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1042\/BST20241633","volume":"53","author":"L Buckley-Benbow","year":"2025","unstructured":"Buckley-Benbow, L., Agnarelli, A. & Bellelli, R. \u201cWhere is my gap\u201d: mechanisms underpinning PARP inhibitor sensitivity in cancer. Biochem. Soc. Trans. 53, 225\u2013234 (2025).","journal-title":"Biochem. Soc. Trans."},{"key":"929_CR64","doi-asserted-by":"publisher","first-page":"268","DOI":"10.1093\/annonc\/mdq322","volume":"22","author":"C Underhill","year":"2011","unstructured":"Underhill, C., Toulmonde, M. & Bonnefoi, H. A review of PARP inhibitors: from bench to bedside. Ann. Oncol. 22, 268\u2013279 (2011).","journal-title":"Ann. Oncol."},{"key":"929_CR65","doi-asserted-by":"publisher","first-page":"1437","DOI":"10.1093\/annonc\/mdz192","volume":"30","author":"J Mateo","year":"2019","unstructured":"Mateo, J. et al. A decade of clinical development of PARP inhibitors in perspective. Ann. Oncol. 30, 1437\u20131447 (2019).","journal-title":"Ann. Oncol."},{"key":"929_CR66","doi-asserted-by":"publisher","first-page":"3759","DOI":"10.1158\/1078-0432.CCR-18-0968","volume":"25","author":"PG Pili\u00e9","year":"2019","unstructured":"Pili\u00e9, P. G., Gay, C. M., Byers, L. A., O\u2019Connor, M. J. & Yap, T. A. PARP inhibitors: extending benefit beyond BRCA-mutant cancers. Clin. Cancer Res. 25, 3759\u20133771 (2019).","journal-title":"Clin. Cancer Res."},{"key":"929_CR67","doi-asserted-by":"publisher","first-page":"297","DOI":"10.2147\/OTT.S499226","volume":"18","author":"M Muzzana","year":"2025","unstructured":"Muzzana, M., Broggini, M. & Damia, G. The landscape of PARP inhibitors in solid cancers. Onco. Targets. Ther. 18, 297\u2013317 (2025).","journal-title":"Onco. Targets. Ther."},{"key":"929_CR68","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1038\/nature14157","volume":"518","author":"PA Mateos-Gomez","year":"2015","unstructured":"Mateos-Gomez, P. A. et al. Mammalian polymerase \u03b8 promotes alternative NHEJ and suppresses recombination. Nature 518, 254\u2013257 (2015).","journal-title":"Nature"},{"key":"929_CR69","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1038\/nature14184","volume":"518","author":"R Ceccaldi","year":"2015","unstructured":"Ceccaldi, R. et al. Homologous-recombination-deficient tumours are dependent on Pol\u03b8-mediated repair. Nature 518, 258\u2013262 (2015).","journal-title":"Nature"},{"key":"929_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12234-1","volume":"10","author":"W Feng","year":"2019","unstructured":"Feng, W. et al. Genetic determinants of cellular addiction to DNA polymerase theta. Nat. Commun. 10, 4286 (2019).","journal-title":"Nat. Commun."},{"key":"929_CR71","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s43018-021-00203-x","volume":"2","author":"J Zhou","year":"2021","unstructured":"Zhou, J. et al. A first-in-class polymerase theta inhibitor selectively targets homologous-recombination-deficient tumors. Nat. Cancer 2, 598\u2013610 (2021).","journal-title":"Nat. Cancer"},{"key":"929_CR72","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.molcel.2018.10.045","volume":"72","author":"KS Lim","year":"2018","unstructured":"Lim, K. S. et al. USP1 is required for replication fork protection in BRCA1-deficient tumors. Mol. Cell 72, 925\u2013941 (2018).","journal-title":"Mol. Cell"},{"key":"929_CR73","doi-asserted-by":"publisher","first-page":"3419","DOI":"10.1158\/0008-5472.CAN-24-0293","volume":"84","author":"L Cadzow","year":"2024","unstructured":"Cadzow, L. et al. The USP1 inhibitor KSQ-4279 overcomes PARP inhibitor resistance in homologous recombination\u2013deficient tumors. Cancer Res. 84, 3419\u20133434 (2024).","journal-title":"Cancer Res."},{"key":"929_CR74","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1038\/s43018-021-00266-w","volume":"2","author":"S Adam","year":"2021","unstructured":"Adam, S. et al. The CIP2A\u2013TOPBP1 axis safeguards chromosome stability and is a synthetic lethal target for BRCA-mutated cancer. Nat. Cancer 2, 1357\u20131371 (2021).","journal-title":"Nat. Cancer"},{"key":"929_CR75","doi-asserted-by":"publisher","first-page":"885","DOI":"10.1016\/j.molcel.2018.12.008","volume":"73","author":"KE Mengwasser","year":"2019","unstructured":"Mengwasser, K. E. et al. Genetic screens reveal FEN1 and APEX2 as BRCA2 synthetic lethal targets. Mol. Cell 73, 885\u2013899 (2019).","journal-title":"Mol. Cell"},{"key":"929_CR76","doi-asserted-by":"publisher","first-page":"1300","DOI":"10.1101\/gad.192856.112","volume":"26","author":"Y Liu-Chittenden","year":"2012","unstructured":"Liu-Chittenden, Y. et al. Genetic and pharmacological disruption of the TEAD\u2013YAP complex suppresses the oncogenic activity of YAP. Genes. Dev. 26, 1300\u20131305 (2012).","journal-title":"Genes. Dev."},{"key":"929_CR77","doi-asserted-by":"publisher","first-page":"1102","DOI":"10.1038\/s43018-024-00754-9","volume":"5","author":"EA Chapeau","year":"2024","unstructured":"Chapeau, E. A. et al. Direct and selective pharmacological disruption of the YAP\u2013TEAD interface by IAG933 inhibits Hippo-dependent and RAS\u2013MAPK-altered cancers. Nat. Cancer 5, 1102\u20131120 (2024).","journal-title":"Nat. Cancer"},{"key":"929_CR78","doi-asserted-by":"publisher","first-page":"E2441","DOI":"10.1073\/pnas.1212021109","volume":"109","author":"JM Lamar","year":"2012","unstructured":"Lamar, J. M. et al. The Hippo pathway target, YAP, promotes metastasis through its TEAD-interaction domain. Proc. Natl Acad. Sci. USA 109, E2441\u2013E2450 (2012).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR79","doi-asserted-by":"publisher","first-page":"e1005465","DOI":"10.1371\/journal.pgen.1005465","volume":"11","author":"C Stein","year":"2015","unstructured":"Stein, C. et al. YAP1 exerts its transcriptional control via TEAD-mediated activation of enhancers. PLoS Genet. 11, e1005465 (2015).","journal-title":"PLoS Genet."},{"key":"929_CR80","doi-asserted-by":"publisher","first-page":"852","DOI":"10.3390\/cancers16050852","volume":"16","author":"R Kanai","year":"2024","unstructured":"Kanai, R., Norton, E., Stern, P., Hynes, R. O. & Lamar, J. M. Identification of a gene signature that predicts dependence upon YAP\/TAZ-TEAD. Cancers 16, 852 (2024).","journal-title":"Cancers"},{"key":"929_CR81","doi-asserted-by":"publisher","first-page":"P216","DOI":"10.1158\/1535-7163.TARG-21-P216","volume":"20","author":"B Amidon","year":"2021","unstructured":"Amidon, B. et al. Abstract P216: IK-930 mediated TEAD inhibition decreases and delays tumor growth and enhances targeted apoptosis in lung and colon cancer xenografts when combined with MEK or EGFR inhibitors. Mol. Cancer Ther. 20, P216\u2013P216 (2021).","journal-title":"Mol. Cancer Ther."},{"key":"929_CR82","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1158\/1535-7163.MCT-22-0681","volume":"23","author":"H Hillen","year":"2024","unstructured":"Hillen, H. et al. A novel irreversible TEAD inhibitor, SWTX-143, blocks Hippo pathway transcriptional output and causes tumor regression in preclinical mesothelioma models. Mol. Cancer Ther. 23, 3\u201313 (2024).","journal-title":"Mol. Cancer Ther."},{"key":"929_CR83","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04029-3","author":"TA Yap","year":"2025","unstructured":"Yap, T. A. et al. YAP\/TEAD inhibitor VT3989 in solid tumors: a phase 1\/2 trial. Nat. Med. https:\/\/doi.org\/10.1038\/s41591-025-04029-3 (2025).","journal-title":"Nat. Med."},{"key":"929_CR84","doi-asserted-by":"publisher","first-page":"S562","DOI":"10.1016\/j.annonc.2025.08.1488","volume":"36","author":"E Garralda","year":"2025","unstructured":"Garralda, E. et al. 919O A first-in-human study of oral IAG933 in adult patients with advanced mesothelioma and other solid tumours. Ann. Oncol. 36, S562 (2025).","journal-title":"Ann. Oncol."},{"key":"929_CR85","unstructured":"US National Library of Medicine. A phase I study of IAG933 in patients with advanced mesothelioma and other solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04857372 (2025)."},{"key":"929_CR86","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S0092-8674(01)00333-6","volume":"105","author":"CJ Potter","year":"2001","unstructured":"Potter, C. J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357\u2013368 (2001).","journal-title":"Cell"},{"key":"929_CR87","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1101\/gad.901101","volume":"15","author":"X Gao","year":"2001","unstructured":"Gao, X. & Pan, D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes. Dev. 15, 1383\u20131392 (2001).","journal-title":"Genes. Dev."},{"key":"929_CR88","doi-asserted-by":"publisher","first-page":"2627","DOI":"10.1101\/gad.239102","volume":"16","author":"T Radimerski","year":"2002","unstructured":"Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. & Thomas, G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes. Dev. 16, 2627\u20132632 (2002).","journal-title":"Genes. Dev."},{"key":"929_CR89","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1056\/NEJMoa1001671","volume":"363","author":"DA Krueger","year":"2010","unstructured":"Krueger, D. A. et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N. Engl. J. Med. 363, 1801\u20131811 (2010).","journal-title":"N. Engl. J. Med."},{"key":"929_CR90","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2025.2472922","author":"DM Ritter","year":"2025","unstructured":"Ritter, D. M., Twardowski, S. & Franz, D. N. Treating subependymal giant cell astrocytoma in patients with tuberous sclerosis complex: an update of the literature. Expert. Rev. Neurother. https:\/\/doi.org\/10.1080\/14737175.2025.2472922 (2025).","journal-title":"Expert. Rev. Neurother."},{"key":"929_CR91","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1126\/science.1226344","volume":"338","author":"G Iyer","year":"2012","unstructured":"Iyer, G. et al. Genome sequencing identifies a basis for everolimus sensitivity. Science 338, 221 (2012).","journal-title":"Science"},{"key":"929_CR92","doi-asserted-by":"publisher","first-page":"e70167","DOI":"10.1002\/ddr.70167","volume":"86","author":"MT Hossain","year":"2025","unstructured":"Hossain, M. T. & Hossain, M. A. Targeting mTOR kinase for cancer treatment: a comprehensive review with clinical insights. Drug. Dev. Res. 86, e70167 (2025).","journal-title":"Drug. Dev. Res."},{"key":"929_CR93","first-page":"43","volume":"7","author":"K Schroeder","year":"2014","unstructured":"Schroeder, K. & Gururangan, S. Molecular variants and mutations in medulloblastoma. Pharmgenomics. Pers. Med. 7, 43\u201351 (2014).","journal-title":"Pharmgenomics. Pers. Med."},{"key":"929_CR94","doi-asserted-by":"publisher","first-page":"2225","DOI":"10.21873\/anticanres.15703","volume":"42","author":"T Sursal","year":"2022","unstructured":"Sursal, T. et al. Molecular stratification of medulloblastoma: clinical outcomes and therapeutic interventions. Anticancer. Res. 42, 2225\u20132239 (2022).","journal-title":"Anticancer. Res."},{"key":"929_CR95","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1038\/nrc2503","volume":"8","author":"EH Epstein","year":"2008","unstructured":"Epstein, E. H. Basal cell carcinomas: attack of the hedgehog. Nat. Rev. Cancer 8, 743\u2013754 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"929_CR96","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1038\/35023008","volume":"406","author":"J Taipale","year":"2000","unstructured":"Taipale, J. et al. Effects of oncogenic mutations in smoothened and patched can be reversed by cyclopamine. Nature 406, 1005\u20131009 (2000).","journal-title":"Nature"},{"key":"929_CR97","doi-asserted-by":"publisher","first-page":"2743","DOI":"10.1101\/gad.1025302","volume":"16","author":"JK Chen","year":"2002","unstructured":"Chen, J. K., Taipale, J., Cooper, M. K. & Beachy, P. A. Inhibition of hedgehog signaling by direct binding of cyclopamine to Smoothened. Genes. Dev. 16, 2743\u20132748 (2002).","journal-title":"Genes. Dev."},{"key":"929_CR98","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1093\/neuonc\/nox109","volume":"19","author":"MW Kieran","year":"2017","unstructured":"Kieran, M. W. et al. Phase I study of oral sonidegib (LDE225) in pediatric brain and solid tumors and a phase II study in children and adults with relapsed medulloblastoma. Neuro. Oncol. 19, 1542\u20131552 (2017).","journal-title":"Neuro. Oncol."},{"key":"929_CR99","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1016\/j.jaad.2016.02.1226","volume":"75","author":"R Dummer","year":"2016","unstructured":"Dummer, R. et al. The 12-month analysis from basal cell carcinoma outcomes with LDE225 treatment (BOLT): a phase II, randomized, double-blind study of sonidegib in patients with advanced basal cell carcinoma. J. Am. Acad. Dermatol. 75, 113\u2013125 (2016).","journal-title":"J. Am. Acad. Dermatol."},{"key":"929_CR100","doi-asserted-by":"publisher","first-page":"2646","DOI":"10.1200\/JCO.2014.60.1591","volume":"33","author":"GW Robinson","year":"2015","unstructured":"Robinson, G. W. et al. Vismodegib exerts targeted efficacy against recurrent sonic hedgehog-subgroup medulloblastoma: results from phase II pediatric brain tumor consortium studies PBTC-025B and PBTC-032. J. Clin. Oncol. 33, 2646\u20132654 (2015).","journal-title":"J. Clin. Oncol."},{"key":"929_CR101","doi-asserted-by":"publisher","first-page":"2180","DOI":"10.1056\/NEJMoa1113538","volume":"366","author":"JY Tang","year":"2012","unstructured":"Tang, J. Y. et al. Inhibiting the hedgehog pathway in patients with the basal-cell nevus syndrome. N. Engl. J. Med. 366, 2180\u20132188 (2012).","journal-title":"N. Engl. J. Med."},{"key":"929_CR102","doi-asserted-by":"publisher","first-page":"716","DOI":"10.1200\/JCO.24.01034","volume":"43","author":"CL Moertel","year":"2025","unstructured":"Moertel, C. L. et al. ReNeu: a pivotal, phase IIb trial of mirdametinib in adults and children with symptomatic neurofibromatosis type 1-associated plexiform neurofibroma. JCO 43, 716\u2013729 (2025).","journal-title":"JCO"},{"key":"929_CR103","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1200\/JCO.20.02220","volume":"39","author":"BD Weiss","year":"2021","unstructured":"Weiss, B. D. et al. NF106: a neurofibromatosis clinical trials consortium phase II trial of the MEK inhibitor mirdametinib (PD-0325901) in adolescents and adults with NF1-related plexiform neurofibromas. J. Clin. Oncol. 39, 797\u2013806 (2021).","journal-title":"J. Clin. Oncol."},{"key":"929_CR104","doi-asserted-by":"publisher","DOI":"10.1200\/PO.22.00421","author":"KB Wisinski","year":"2023","unstructured":"Wisinski, K. B. et al. Trametinib in patients with NF1-, GNAQ-, or GNA11-mutant tumors: results from the NCI-MATCH ECOG-ACRIN trial (EAY131) subprotocols S1 and S2. JCO Precis. Oncol. https:\/\/doi.org\/10.1200\/PO.22.00421 (2023).","journal-title":"JCO Precis. Oncol."},{"key":"929_CR105","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1038\/nrc2502","volume":"8","author":"WG Kaelin","year":"2008","unstructured":"Kaelin, W. G. The von Hippel-Lindau tumour suppressor protein: O2 sensing and cancer. Nat. Rev. Cancer 8, 865\u2013873 (2008).","journal-title":"Nat. Rev. Cancer"},{"key":"929_CR106","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1056\/NEJMoa2313906","volume":"391","author":"TK Choueiri","year":"2024","unstructured":"Choueiri, T. K. et al. Belzutifan versus everolimus for advanced renal-cell carcinoma. N. Engl. J. Med. 391, 710\u2013721 (2024).","journal-title":"N. Engl. J. Med."},{"key":"929_CR107","doi-asserted-by":"publisher","first-page":"2036","DOI":"10.1056\/NEJMoa2103425","volume":"385","author":"E Jonasch","year":"2021","unstructured":"Jonasch, E. et al. Belzutifan for renal cell carcinoma in von Hippel-Lindau disease. N. Engl. J. Med. 385, 2036\u20132046 (2021).","journal-title":"N. Engl. J. Med."},{"key":"929_CR108","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1158\/1078-0432.CCR-15-2631","volume":"22","author":"DJ Kwiatkowski","year":"2016","unstructured":"Kwiatkowski, D. J. et al. Mutations in TSC1, TSC2, and MTOR are associated with response to rapalogs in patients with metastatic renal cell carcinoma. Clin. Cancer Res. 22, 2445\u20132452 (2016).","journal-title":"Clin. Cancer Res."},{"key":"929_CR109","doi-asserted-by":"crossref","unstructured":"First drug approved for neurofibromas is a MEK inhibitor. Nat. Biotechnol. 38, 513 (2020).","DOI":"10.1038\/s41587-020-0530-3"},{"key":"929_CR110","doi-asserted-by":"publisher","first-page":"2171","DOI":"10.1056\/NEJMoa1113713","volume":"366","author":"A Sekulic","year":"2012","unstructured":"Sekulic, A. et al. Efficacy and safety of vismodegib in advanced basal-cell carcinoma. N. Engl. J. Med. 366, 2171\u20132179 (2012).","journal-title":"N. Engl. J. Med."},{"key":"929_CR111","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1016\/S1470-2045(17)30072-4","volume":"18","author":"B Dr\u00e9no","year":"2017","unstructured":"Dr\u00e9no, B. et al. Two intermittent vismodegib dosing regimens in patients with multiple basal-cell carcinomas (MIKIE): a randomised, regimen-controlled, double-blind, phase 2 trial. Lancet Oncol. 18, 404\u2013412 (2017).","journal-title":"Lancet Oncol."},{"key":"929_CR112","doi-asserted-by":"publisher","first-page":"17135","DOI":"10.1073\/pnas.1104182108","volume":"108","author":"A Scholer-Dahirel","year":"2011","unstructured":"Scholer-Dahirel, A. et al. Maintenance of adenomatous polyposis coli (APC)-mutant colorectal cancer is dependent on Wnt\/beta-catenin signaling. Proc. Natl Acad. Sci. USA 108, 17135\u201317140 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR113","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4463","volume":"5","author":"Z Lu","year":"2014","unstructured":"Lu, Z. et al. Skp2 suppresses apoptosis in Rb1-deficient tumours by limiting E2F1 activity. Nat. Commun. 5, 3463 (2014).","journal-title":"Nat. Commun."},{"key":"929_CR114","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1038\/s41416-022-01898-0","volume":"127","author":"P Gupta","year":"2022","unstructured":"Gupta, P., Zhao, H., Hoang, B. & Schwartz, E. L. Targeting the untargetable: RB1-deficient tumours are vulnerable to Skp2 ubiquitin ligase inhibition. Br. J. Cancer 127, 969\u2013975 (2022).","journal-title":"Br. J. Cancer"},{"key":"929_CR115","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.1126\/science.aad5214","volume":"351","author":"GV Kryukov","year":"2016","unstructured":"Kryukov, G. V. et al. MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells. Science 351, 1214\u20131218 (2016).","journal-title":"Science"},{"key":"929_CR116","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.1126\/science.aad5944","volume":"351","author":"KJ Mavrakis","year":"2016","unstructured":"Mavrakis, K. J. et al. Disordered methionine metabolism in MTAP\/CDKN2A-deleted cancers leads to dependence on PRMT5. Science 351, 1208\u20131213 (2016).","journal-title":"Science"},{"key":"929_CR117","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1016\/j.celrep.2016.03.043","volume":"15","author":"K Marjon","year":"2016","unstructured":"Marjon, K. et al. MTAP deletions in cancer create vulnerability to targeting of the MAT2A\/PRMT5\/RIOK1 axis. Cell Rep. 15, 574\u2013587 (2016).","journal-title":"Cell Rep."},{"key":"929_CR118","doi-asserted-by":"publisher","first-page":"58","DOI":"10.36401\/JIPO-22-1","volume":"5","author":"K Feustel","year":"2022","unstructured":"Feustel, K. & Falchook, G. S. Protein arginine methyltransferase 5 (PRMT5) inhibitors in oncology clinical trials: a review. J. Immunother. Precis. Oncol. 5, 58\u201367 (2022).","journal-title":"J. Immunother. Precis. Oncol."},{"key":"929_CR119","doi-asserted-by":"publisher","first-page":"108493","DOI":"10.1016\/j.celrep.2020.108493","volume":"33","author":"JE Neggers","year":"2020","unstructured":"Neggers, J. E. et al. Synthetic lethal interaction between the ESCRT paralog enzymes VPS4A and VPS4B in cancers harboring loss of chromosome 18q or 16q. Cell Rep. 33, 108493 (2020).","journal-title":"Cell Rep."},{"key":"929_CR120","doi-asserted-by":"publisher","first-page":"e10812","DOI":"10.15252\/emmm.201910812","volume":"12","author":"E Szyma\u0144ska","year":"2020","unstructured":"Szyma\u0144ska, E. et al. Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer. EMBO Mol. Med. 12, e10812 (2020).","journal-title":"EMBO Mol. Med."},{"key":"929_CR121","doi-asserted-by":"publisher","first-page":"R50","DOI":"10.1093\/hmg\/ddm018","volume":"16","author":"M Esteller","year":"2007","unstructured":"Esteller, M. Epigenetic gene silencing in cancer: the DNA hypermethylome. Hum. Mol. Genet. 16, R50\u2013R59 (2007).","journal-title":"Hum. Mol. Genet."},{"key":"929_CR122","doi-asserted-by":"publisher","first-page":"4709","DOI":"10.1158\/0008-5472.CAN-21-0774","volume":"81","author":"K Nesic","year":"2021","unstructured":"Nesic, K. et al. Acquired RAD51C promoter methylation loss causes PARP inhibitor resistance in high-grade serous ovarian carcinoma. Cancer Res. 81, 4709\u20134722 (2021).","journal-title":"Cancer Res."},{"key":"929_CR123","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.ygyno.2017.03.034","volume":"145","author":"EM Swisher","year":"2017","unstructured":"Swisher, E. M. et al. BRCA1 and RAD51C promoter hypermethylation confer sensitivity to the PARP inhibitor rucaparib in patients with relapsed, platinum-sensitive ovarian carcinoma in ARIEL2 Part 1. Gynecol. Oncol. 145, 5 (2017).","journal-title":"Gynecol. Oncol."},{"key":"929_CR124","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-05564-z","volume":"9","author":"O Kondrashova","year":"2018","unstructured":"Kondrashova, O. et al. Methylation of all BRCA1 copies predicts response to the PARP inhibitor rucaparib in ovarian carcinoma. Nat. Commun. 9, 3970 (2018).","journal-title":"Nat. Commun."},{"key":"929_CR125","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/ng.2699","volume":"45","author":"Y Sato","year":"2013","unstructured":"Sato, Y. et al. Integrated molecular analysis of clear-cell renal cell carcinoma. Nat. Genet. 45, 860\u2013867 (2013).","journal-title":"Nat. Genet."},{"key":"929_CR126","doi-asserted-by":"publisher","first-page":"850","DOI":"10.1038\/s41591-019-0404-8","volume":"25","author":"H Li","year":"2019","unstructured":"Li, H. et al. The landscape of cancer cell line metabolism. Nat. Med. 25, 850\u2013860 (2019).","journal-title":"Nat. Med."},{"key":"929_CR127","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.83","volume":"3","author":"B Delage","year":"2012","unstructured":"Delage, B. et al. Promoter methylation of argininosuccinate synthetase-1 sensitises lymphomas to arginine deiminase treatment, autophagy and caspase-dependent apoptosis. Cell Death Dis. 3, e342 (2012).","journal-title":"Cell Death Dis."},{"key":"929_CR128","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2012.197","volume":"4","author":"N Syed","year":"2013","unstructured":"Syed, N. et al. Epigenetic status of argininosuccinate synthetase and argininosuccinate lyase modulates autophagy and cell death in glioblastoma. Cell Death Dis. 4, e458 (2013).","journal-title":"Cell Death Dis."},{"key":"929_CR129","doi-asserted-by":"publisher","first-page":"1161","DOI":"10.1016\/j.chembiol.2017.08.028","volume":"24","author":"A Luengo","year":"2017","unstructured":"Luengo, A., Gui, D. Y. & Vander Heiden, M. G. Targeting metabolism for cancer therapy. Cell Chem. Biol. 24, 1161\u20131180 (2017).","journal-title":"Cell Chem. Biol."},{"key":"929_CR130","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1038\/nrm2858","volume":"11","author":"S Negrini","year":"2010","unstructured":"Negrini, S., Gorgoulis, V. G. & Halazonetis, T. D. Genomic instability \u2014 an evolving hallmark of cancer. Nat. Rev. Mol. Cell Biol. 11, 220\u2013228 (2010).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"929_CR131","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1038\/s41586-019-1102-x","volume":"568","author":"EM Chan","year":"2019","unstructured":"Chan, E. M. et al. WRN helicase is a synthetic lethal target in microsatellite unstable cancers. Nature 568, 551\u2013556 (2019).","journal-title":"Nature"},{"key":"929_CR132","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1016\/j.isci.2019.02.006","volume":"13","author":"L Kategaya","year":"2019","unstructured":"Kategaya, L., Perumal, S. K., Hager, J. H. & Belmont, L. D. Werner syndrome helicase is required for the survival of cancer cells with microsatellite instability. iScience 13, 488\u2013497 (2019).","journal-title":"iScience"},{"key":"929_CR133","doi-asserted-by":"publisher","first-page":"S496","DOI":"10.1016\/j.annonc.2023.09.1905","volume":"34","author":"M Moschetta","year":"2023","unstructured":"Moschetta, M. et al. 719TiP A phase I\/Ib study of the Werner (WRN) helicase inhibitor HRO761 as single agent and in combination with irinotecan or tislelizumab in patients with microsatellite instability-high (MSIhi) or mismatch repair deficient (dMMR) advanced solid tumors. Ann. Oncol. 34, S496 (2023).","journal-title":"Ann. Oncol."},{"key":"929_CR134","doi-asserted-by":"publisher","first-page":"443","DOI":"10.1038\/s41586-024-07350-y","volume":"629","author":"S Ferretti","year":"2024","unstructured":"Ferretti, S. et al. Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers. Nature 629, 443\u2013449 (2024).","journal-title":"Nature"},{"key":"929_CR135","doi-asserted-by":"publisher","first-page":"S567","DOI":"10.1016\/j.annonc.2025.08.1494","volume":"36","author":"MBB Foote","year":"2025","unstructured":"Foote, M. B. B. et al. 925MO First-in-human phase I\/Ib study of the oral Werner (WRN) helicase inhibitor HRO761 in patients (pts) with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) advanced solid tumors: Interim safety and efficacy analysis from HRO761 single agent dose escalation. Ann. Oncol. 36, S567\u2013S568 (2025).","journal-title":"Ann. Oncol."},{"key":"929_CR136","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1038\/s41576-019-0171-x","volume":"21","author":"U Ben-David","year":"2020","unstructured":"Ben-David, U. & Amon, A. Context is everything: aneuploidy in cancer. Nat. Rev. Genet. 21, 44\u201362 (2020).","journal-title":"Nat. Rev. Genet."},{"key":"929_CR137","doi-asserted-by":"publisher","first-page":"2014","DOI":"10.1038\/s41588-024-01916-2","volume":"56","author":"E Sdeor","year":"2024","unstructured":"Sdeor, E., Okada, H., Saad, R., Ben-Yishay, T. & Ben-David, U. Aneuploidy as a driver of human cancer. Nat. Genet. 56, 2014\u20132026 (2024).","journal-title":"Nat. Genet."},{"key":"929_CR138","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1038\/s41586-020-03114-6","volume":"590","author":"Y Cohen-Sharir","year":"2021","unstructured":"Cohen-Sharir, Y. et al. Aneuploidy renders cancer cells vulnerable to mitotic checkpoint inhibition. Nature 590, 486\u2013491 (2021).","journal-title":"Nature"},{"key":"929_CR139","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21447-2","volume":"12","author":"C Marquis","year":"2021","unstructured":"Marquis, C. et al. Chromosomally unstable tumor cells specifically require KIF18A for proliferation. Nat. Commun. 12, 1213 (2021).","journal-title":"Nat. Commun."},{"key":"929_CR140","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55300-z","volume":"16","author":"AF Phillips","year":"2025","unstructured":"Phillips, A. F. et al. Targeting chromosomally unstable tumors with a selective KIF18A inhibitor. Nat. Commun. 16, 307 (2025).","journal-title":"Nat. Commun."},{"key":"929_CR141","doi-asserted-by":"publisher","first-page":"TPS3181","DOI":"10.1200\/JCO.2024.42.16_suppl.TPS3181","volume":"42","author":"S Gaillard","year":"2024","unstructured":"Gaillard, S. et al. A phase I\/II, first-in-human study of VLS-1488, an oral KIF18A inhibitor, in patients with advanced cancer. JCO 42, TPS3181\u2013TPS3181 (2024).","journal-title":"JCO"},{"key":"929_CR142","unstructured":"US National Library of Medicine. First-in-human study of ATX-295, an oral inhibitor of KIF18A, in patients with advanced or metastatic solid tumors, including ovarian cancer. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06799065 (2025)."},{"key":"929_CR143","unstructured":"US National Library of Medicine. A study of sovilnesib in subjects with ovarian cancer. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06084416 (2024)."},{"key":"929_CR144","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41392-021-00648-7","volume":"6","author":"R Huang","year":"2021","unstructured":"Huang, R. & Zhou, P.-K. DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy. Sig Transduct. Target. Ther. 6, 1\u201335 (2021).","journal-title":"Sig Transduct. Target. Ther."},{"key":"929_CR145","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1016\/j.molcel.2022.04.023","volume":"82","author":"K Cong","year":"2022","unstructured":"Cong, K. & Cantor, S. B. Exploiting replication gaps for cancer therapy. Mol. Cell 82, 2363\u20132369 (2022).","journal-title":"Mol. Cell"},{"key":"929_CR146","doi-asserted-by":"publisher","first-page":"4664","DOI":"10.1016\/j.molcel.2022.11.008","volume":"82","author":"O Belan","year":"2022","unstructured":"Belan, O. et al. POLQ seals post-replicative ssDNA gaps to maintain genome stability in BRCA-deficient cancer cells. Mol. Cell 82, 4664\u20134680 (2022).","journal-title":"Mol. Cell"},{"key":"929_CR147","doi-asserted-by":"publisher","first-page":"4218","DOI":"10.1016\/j.molcel.2022.09.013","volume":"82","author":"A Mann","year":"2022","unstructured":"Mann, A. et al. POL\u03b8 prevents MRE11-NBS1-CtIP-dependent fork breakage in the absence of BRCA2\/RAD51 by filling lagging-strand gaps. Mol. Cell 82, 4218\u20134231 (2022).","journal-title":"Mol. Cell"},{"key":"929_CR148","doi-asserted-by":"publisher","first-page":"111716","DOI":"10.1016\/j.celrep.2022.111716","volume":"41","author":"A Schrempf","year":"2022","unstructured":"Schrempf, A. et al. POL\u03b8 processes ssDNA gaps and promotes replication fork progression in BRCA1-deficient cells. Cell Rep. 41, 111716 (2022).","journal-title":"Cell Rep."},{"key":"929_CR149","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1038\/s41586-020-2769-8","volume":"586","author":"N van Wietmarschen","year":"2020","unstructured":"van Wietmarschen, N. et al. Repeat expansions confer WRN dependence in microsatellite-unstable cancers. Nature 586, 292\u2013298 (2020).","journal-title":"Nature"},{"key":"929_CR150","doi-asserted-by":"publisher","first-page":"e175369","DOI":"10.1172\/JCI175369","volume":"134","author":"MT Dillon","year":"2024","unstructured":"Dillon, M. T. et al. Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation. J. Clin. Invest. 134, e175369 (2024).","journal-title":"J. Clin. Invest."},{"key":"929_CR151","first-page":"PO.20.00439","volume":"5","author":"H Mahdi","year":"2021","unstructured":"Mahdi, H. et al. Ceralasertib-mediated ATR inhibition combined with olaparib in advanced cancers harboring DNA damage response and repair alterations (Olaparib Combinations). JCO Precis. Oncol. 5, PO.20.00439 (2021).","journal-title":"JCO Precis. Oncol."},{"key":"929_CR152","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1038\/s41416-021-01405-x","volume":"125","author":"MR Middleton","year":"2021","unstructured":"Middleton, M. R. et al. Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine\u2009\u00b1\u2009cisplatin in patients with advanced solid tumours. Br. J. Cancer 125, 510\u2013519 (2021).","journal-title":"Br. J. Cancer"},{"key":"929_CR153","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1007\/s10637-022-01216-8","volume":"40","author":"SN Waqar","year":"2022","unstructured":"Waqar, S. N. et al. Phase I trial of ATM inhibitor M3541 in combination with palliative radiotherapy in patients with solid tumors. Invest. N. Drugs 40, 596\u2013605 (2022).","journal-title":"Invest. N. Drugs"},{"key":"929_CR154","doi-asserted-by":"publisher","DOI":"10.1007\/s11912-021-01098-8","volume":"23","author":"A Kong","year":"2021","unstructured":"Kong, A. & Mehanna, H. WEE1 inhibitor: clinical development. Curr. Oncol. Rep. 23, 107 (2021).","journal-title":"Curr. Oncol. Rep."},{"key":"929_CR155","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1007\/s10637-023-01371-6","volume":"41","author":"GS Falchook","year":"2023","unstructured":"Falchook, G. S. et al. A phase Ib study of adavosertib, a selective Wee1 inhibitor, in patients with locally advanced or metastatic solid tumors. Invest. N. Drugs 41, 493\u2013502 (2023).","journal-title":"Invest. N. Drugs"},{"key":"929_CR156","doi-asserted-by":"publisher","first-page":"6093","DOI":"10.1158\/1538-7445.AM2023-6093","volume":"83","author":"M Abed","year":"2023","unstructured":"Abed, M. et al. Abstract 6093: IDE161, a potential first-in-class clinical candidate PARG inhibitor, selectively targets homologous-recombination-deficient and PARP inhibitor resistant breast and ovarian tumors. Cancer Res. 83, 6093 (2023).","journal-title":"Cancer Res."},{"key":"929_CR157","doi-asserted-by":"publisher","first-page":"3084","DOI":"10.1200\/JCO.2022.40.16_suppl.3084","volume":"40","author":"RC Lynch","year":"2022","unstructured":"Lynch, R. C. et al. Phase 1 results of a phase 1\/2 trial of CYT-0851, a first-in-class inhibitor of RAD51-mediated homologous recombination, in patients with advanced solid and hematologic cancers. JCO 40, 3084\u20133084 (2022).","journal-title":"JCO"},{"key":"929_CR158","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1038\/s41416-020-01151-6","volume":"124","author":"MTJ van Bussel","year":"2021","unstructured":"van Bussel, M. T. J. et al. A first-in-man phase 1 study of the DNA-dependent protein kinase inhibitor peposertib (formerly M3814) in patients with advanced solid tumours. Br. J. Cancer 124, 728\u2013735 (2021).","journal-title":"Br. J. Cancer"},{"key":"929_CR159","doi-asserted-by":"publisher","first-page":"101","DOI":"10.1016\/j.blre.2010.03.002","volume":"24","author":"A Shimamura","year":"2010","unstructured":"Shimamura, A. & Alter, B. P. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev. 24, 101\u2013122 (2010).","journal-title":"Blood Rev."},{"key":"929_CR160","doi-asserted-by":"publisher","first-page":"4354","DOI":"10.1200\/JCO.2016.67.5942","volume":"34","author":"S Leijen","year":"2016","unstructured":"Leijen, S. et al. Phase II study of WEE1 inhibitor AZD1775 plus carboplatin in patients with TP53-mutated ovarian cancer refractory or resistant to first-line therapy within 3 months. JCO 34, 4354\u20134361 (2016).","journal-title":"JCO"},{"key":"929_CR161","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1038\/s41416-021-01406-w","volume":"125","author":"GI Shapiro","year":"2021","unstructured":"Shapiro, G. I. et al. Phase 1 study of the ATR inhibitor berzosertib in combination with cisplatin in patients with advanced solid tumours. Br. J. Cancer 125, 520\u2013527 (2021).","journal-title":"Br. J. Cancer"},{"key":"929_CR162","doi-asserted-by":"publisher","first-page":"953","DOI":"10.3390\/cancers14040953","volume":"14","author":"F Martorana","year":"2022","unstructured":"Martorana, F., Da Silva, L. A., Sessa, C. & Colombo, I. Everything comes with a price: the toxicity profile of DNA-damage response targeting agents. Cancers 14, 953 (2022).","journal-title":"Cancers"},{"key":"929_CR163","doi-asserted-by":"publisher","first-page":"3104","DOI":"10.1200\/JCO.2023.41.16_suppl.3104","volume":"41","author":"E Maldonado","year":"2023","unstructured":"Maldonado, E. et al. A phase 2 study of the WEE1 inhibitor AZD1775 in SETD2-deficient advanced solid tumor malignancies. J. Clin. Oncol. 41, 3104\u20133104 (2023).","journal-title":"J. Clin. Oncol."},{"key":"929_CR164","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/40618","volume":"388","author":"MA Nowak","year":"1997","unstructured":"Nowak, M. A., Boerlijst, M. C., Cooke, J. & Smith, J. M. Evolution of genetic redundancy. Nature 388, 167\u2013171 (1997).","journal-title":"Nature"},{"key":"929_CR165","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1038\/s41568-024-00763-x","volume":"25","author":"R Arafeh","year":"2025","unstructured":"Arafeh, R., Shibue, T., Dempster, J. M., Hahn, W. C. & Vazquez, F. The present and future of the Cancer Dependency Map. Nat. Rev. Cancer 25, 59\u201373 (2025).","journal-title":"Nat. Rev. Cancer"},{"key":"929_CR166","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.trecan.2023.02.002","volume":"9","author":"CJ Ryan","year":"2023","unstructured":"Ryan, C. J., Mehta, I., Kebabci, N. & Adams, D. J. Targeting synthetic lethal paralogs in cancer. Trends Cancer 9, 397\u2013409 (2023).","journal-title":"Trends Cancer"},{"key":"929_CR167","doi-asserted-by":"publisher","first-page":"e8871","DOI":"10.15252\/msb.20198871","volume":"15","author":"R Dandage","year":"2019","unstructured":"Dandage, R. & Landry, C. R. Paralog dependency indirectly affects the robustness of human cells. Mol. Syst. Biol. 15, e8871 (2019).","journal-title":"Mol. Syst. Biol."},{"key":"929_CR168","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nm.3480","volume":"20","author":"KC Helming","year":"2014","unstructured":"Helming, K. C. et al. ARID1B is a specific vulnerability in ARID1A-mutant cancers. Nat. Med. 20, 251\u20134 (2014). This study demonstrated that cancers deficient in the SWI\/SNF subunit ARID1A depend on its paralogue, ARID1B.","journal-title":"Nat. Med."},{"key":"929_CR169","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34562-5","volume":"13","author":"J Cantley","year":"2022","unstructured":"Cantley, J. et al. Selective PROTAC-mediated degradation of SMARCA2 is efficacious in SMARCA4 mutant cancers. Nat. Commun. 13, 6814 (2022).","journal-title":"Nat. Commun."},{"key":"929_CR170","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1073\/pnas.1316793111","volume":"111","author":"GR Hoffman","year":"2014","unstructured":"Hoffman, G. R. et al. Functional epigenetics approach identifies BRM\/SMARCA2 as a critical synthetic lethal target in BRG1-deficient cancers. Proc. Natl Acad. Sci. USA 111, 2\u20137 (2014).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR171","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1158\/2159-8290.CD-15-0754","volume":"6","author":"H Ogiwara","year":"2016","unstructured":"Ogiwara, H. et al. Targeting p300 addiction in CBP-deficient cancers causes synthetic lethality by apoptotic cell death due to abrogation of MYC expression. Cancer Discov. 6, 430\u2013445 (2016).","journal-title":"Cancer Discov."},{"key":"929_CR172","doi-asserted-by":"publisher","first-page":"e26980","DOI":"10.7554\/eLife.26980","volume":"6","author":"P van der Lelij","year":"2017","unstructured":"van der Lelij, P. et al. Synthetic lethality between the cohesin subunits STAG1 and STAG2 in diverse cancer contexts. eLife 6, e26980 (2017).","journal-title":"eLife"},{"key":"929_CR173","doi-asserted-by":"publisher","first-page":"37619","DOI":"10.18632\/oncotarget.16838","volume":"8","author":"L Benedetti","year":"2017","unstructured":"Benedetti, L., Cereda, M., Monteverde, L., Desai, N. & Ciccarelli, F. D. Synthetic lethal interaction between the tumour suppressor STAG2 and its paralog STAG1. Oncotarget 8, 37619\u201337632 (2017).","journal-title":"Oncotarget"},{"key":"929_CR174","doi-asserted-by":"publisher","first-page":"e142149","DOI":"10.1172\/jci.insight.142149","volume":"6","author":"Z Tothova","year":"2021","unstructured":"Tothova, Z. et al. Cohesin mutations alter DNA damage repair and chromatin structure and create therapeutic vulnerabilities in MDS\/AML. JCI Insight 6, e142149 (2021).","journal-title":"JCI Insight"},{"key":"929_CR175","doi-asserted-by":"publisher","first-page":"937","DOI":"10.1038\/s41588-018-0155-3","volume":"50","author":"SR Viswanathan","year":"2018","unstructured":"Viswanathan, S. R. et al. Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer. Nat. Genet. 50, 937\u2013943 (2018).","journal-title":"Nat. Genet."},{"key":"929_CR176","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1038\/s41586-024-08509-3","volume":"638","author":"PC Borck","year":"2025","unstructured":"Borck, P. C. et al. SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO. Nature 638, 1104\u20131111\u00a0(2025).","journal-title":"Nature"},{"key":"929_CR177","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1038\/s41586-024-08398-6","volume":"638","author":"V Prindle","year":"2025","unstructured":"Prindle, V. et al. Synthetic lethality of mRNA quality control complexes in cancer. Nature 638, 1095\u20131103 (2025).","journal-title":"Nature"},{"key":"929_CR178","doi-asserted-by":"publisher","first-page":"120070","DOI":"10.1016\/j.bbamcr.2025.120070","volume":"1873","author":"H Zhang","year":"2025","unstructured":"Zhang, H. et al. Tumor suppressor collateral damage screens reveal mRNA homeostasis protein HBS1L as a novel vulnerability in ch9p21 driven FOCAD deleted cancer. Biochim. Biophys. Acta Mol. Cell Res. 1873, 120070 (2025).","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"929_CR179","doi-asserted-by":"publisher","first-page":"B027","DOI":"10.1158\/1535-7163.TARG-25-B027","volume":"24","author":"K Lazarides","year":"2025","unstructured":"Lazarides, K. et al. Abstract B027: TNG961: a selective oral molecular glue degrader of HBS1L inducing tumor regression in na\u00efve and PRMT5i-refractory FOCAD-deleted models. Mol. Cancer Ther. 24, B027\u2013B027 (2025).","journal-title":"Mol. Cancer Ther."},{"key":"929_CR180","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1038\/nature11331","volume":"488","author":"FL Muller","year":"2012","unstructured":"Muller, F. L. et al. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature 488, 337\u2013342 (2012).","journal-title":"Nature"},{"key":"929_CR181","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/s42255-020-00313-3","volume":"2","author":"Y-H Lin","year":"2020","unstructured":"Lin, Y.-H. et al. An enolase inhibitor for the targeted treatment of ENO1-deleted cancers. Nat. Metab. 2, 1413\u20131426 (2020).","journal-title":"Nat. Metab."},{"key":"929_CR182","doi-asserted-by":"publisher","first-page":"13813","DOI":"10.1021\/acs.jmedchem.2c01039","volume":"65","author":"VC Yan","year":"2022","unstructured":"Yan, V. C. et al. Prodrugs of a 1-hydroxy-2-oxopiperidin-3-yl phosphonate enolase inhibitor for the treatment of ENO1-deleted cancers. J. Med. Chem. 65, 13813\u201313832 (2022).","journal-title":"J. Med. Chem."},{"key":"929_CR183","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s40170-021-00259-4","volume":"9","author":"S Khadka","year":"2021","unstructured":"Khadka, S. et al. Impaired anaplerosis is a major contributor to glycolysis inhibitor toxicity in glioma. Cancer Metab. 9, 27 (2021).","journal-title":"Cancer Metab."},{"key":"929_CR184","doi-asserted-by":"publisher","first-page":"546","DOI":"10.1097\/CCO.0000000000000870","volume":"34","author":"J Guo","year":"2022","unstructured":"Guo, J., Yang, Y., Buettner, R. & Rosen, S. T. Targeting the methionine-methionine adenosyl transferase 2A-S-adenosyl methionine axis for cancer therapy. Curr. Opin. Oncol. 34, 546\u2013551 (2022).","journal-title":"Curr. Opin. Oncol."},{"key":"929_CR185","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/s41416-023-02276-0","volume":"129","author":"AB El-Khoueiry","year":"2023","unstructured":"El-Khoueiry, A. B. et al. Phase 1 study of GSK3368715, a type I PRMT inhibitor, in patients with advanced solid tumors. Br. J. Cancer 129, 309\u2013317 (2023).","journal-title":"Br. J. Cancer"},{"key":"929_CR186","doi-asserted-by":"publisher","first-page":"3019","DOI":"10.1200\/JCO.2021.39.15_suppl.3019","volume":"39","author":"J Rodon Ahnert","year":"2021","unstructured":"Rodon Ahnert, J. et al. PF-06939999, a potent and selective PRMT5 inhibitor, in patients with advanced or metastatic solid tumors: a phase 1 dose escalation study. JCO 39, 3019\u20133019 (2021).","journal-title":"JCO"},{"key":"929_CR187","doi-asserted-by":"publisher","first-page":"2310","DOI":"10.1158\/2159-8290.CD-23-0951","volume":"13","author":"KM Mulvaney","year":"2023","unstructured":"Mulvaney, K. M. Early clinical success of MTA-cooperative PRMT5 inhibitors for the treatment of CDKN2A\/MTAP-deleted cancers. Cancer Discov. 13, 2310\u20132312 (2023).","journal-title":"Cancer Discov."},{"key":"929_CR188","doi-asserted-by":"publisher","first-page":"PR006","DOI":"10.1158\/1535-7163.TARG-23-PR006","volume":"22","author":"J Rodon","year":"2023","unstructured":"Rodon, J. et al. Abstract PR006: Initial results from first-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in biomarker-selected solid tumors. Mol. Cancer Therapeutics 22, PR006 (2023).","journal-title":"Mol. Cancer Therapeutics"},{"key":"929_CR189","doi-asserted-by":"publisher","first-page":"102264","DOI":"10.1016\/j.tranon.2024.102264","volume":"52","author":"KJ Briggs","year":"2025","unstructured":"Briggs, K. J. et al. TNG908 is a brain-penetrant, MTA-cooperative PRMT5 inhibitor developed for the treatment of MTAP-deleted cancers. Transl. Oncol. 52, 102264 (2025).","journal-title":"Transl. Oncol."},{"key":"929_CR190","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-55316-5","volume":"16","author":"M Gounder","year":"2025","unstructured":"Gounder, M. et al. MAT2A inhibitor AG-270\/S095033 in patients with advanced malignancies: a phase I trial. Nat. Commun. 16, 423 (2025).","journal-title":"Nat. Commun."},{"key":"929_CR191","doi-asserted-by":"publisher","first-page":"PR03","DOI":"10.1158\/1535-7163.TARG-19-PR03","volume":"18","author":"RS Heist","year":"2019","unstructured":"Heist, R. S. et al. Abstract PR03: A phase 1 trial of AG-270 in patients with advanced solid tumors or lymphoma with homozygous MTAP deletion. Mol. Cancer Ther. 18, PR03\u2013PR03 (2019).","journal-title":"Mol. Cancer Ther."},{"key":"929_CR192","doi-asserted-by":"publisher","first-page":"B027","DOI":"10.1158\/1557-3265.BLADDER24-B027","volume":"30","author":"CL Neilan","year":"2024","unstructured":"Neilan, C. L. et al. Abstract B027: The MAT2A inhibitor IDE397: a novel combination backbone for urothelial cancer subjects with MTAP deficiency. Clin. Cancer Res. 30, B027\u2013B027 (2024).","journal-title":"Clin. Cancer Res."},{"key":"929_CR193","unstructured":"US National Library of Medicine. A phase 1\/2 study of AMG 193 in combination with IDE397 in participants with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05975073 (2023)."},{"key":"929_CR194","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1038\/nature10363","volume":"477","author":"C Frezza","year":"2011","unstructured":"Frezza, C. et al. Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase. Nature 477, 225\u2013228 (2011).","journal-title":"Nature"},{"key":"929_CR195","doi-asserted-by":"publisher","first-page":"524","DOI":"10.1016\/j.ccr.2011.09.006","volume":"20","author":"J Adam","year":"2011","unstructured":"Adam, J. et al. Renal cyst formation in Fh1-deficient mice is independent of the Hif\/Phd pathway: roles for fumarate in KEAP1 succination and Nrf2 signaling. Cancer Cell 20, 524\u2013537 (2011).","journal-title":"Cancer Cell"},{"key":"929_CR196","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.ccr.2011.10.005","volume":"20","author":"L Kinch","year":"2011","unstructured":"Kinch, L., Grishin, N. V. & Brugarolas, J. Succination of Keap1 and activation of Nrf2-dependent antioxidant pathways in FH-deficient papillary renal cell carcinoma type 2. Cancer Cell 20, 418\u2013420 (2011).","journal-title":"Cancer Cell"},{"key":"929_CR197","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3390\/biom10010143","volume":"10","author":"P Podkalicka","year":"2020","unstructured":"Podkalicka, P. et al. Synthetically lethal interactions of heme oxygenase-1 and fumarate hydratase genes. Biomolecules 10, 143 (2020).","journal-title":"Biomolecules"},{"key":"929_CR198","doi-asserted-by":"publisher","first-page":"4551","DOI":"10.1016\/j.celrep.2020.03.022","volume":"30","author":"A Morin","year":"2020","unstructured":"Morin, A. et al. TET-mediated hypermethylation primes SDH-deficient cells for HIF2\u03b1-driven mesenchymal transition. Cell Rep. 30, 4551\u20134566 (2020).","journal-title":"Cell Rep."},{"key":"929_CR199","doi-asserted-by":"publisher","first-page":"739","DOI":"10.1016\/j.ccr.2013.04.018","volume":"23","author":"E Letouz\u00e9","year":"2013","unstructured":"Letouz\u00e9, E. et al. SDH mutations establish a hypermethylator phenotype in paraganglioma. Cancer Cell 23, 739\u2013752 (2013).","journal-title":"Cancer Cell"},{"key":"929_CR200","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1158\/1078-0432.CCR-23-2234","volume":"30","author":"A Woods","year":"2024","unstructured":"Woods, A. et al. FDA approval summary: Ivosidenib in combination with azacitidine for treatment of patients with newly diagnosed acute myeloid leukemia with an IDH1 mutation. Clin. Cancer Res. 30, 1226\u20131231 (2024).","journal-title":"Clin. Cancer Res."},{"key":"929_CR201","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1038\/s41586-022-04928-2","volume":"609","author":"JJ Kwon","year":"2022","unstructured":"Kwon, J. J. et al. Structure\u2013function analysis of the SHOC2\u2013MRAS\u2013PP1C holophosphatase complex. Nature 609, 408\u2013415 (2022).","journal-title":"Nature"},{"key":"929_CR202","doi-asserted-by":"publisher","first-page":"e2006800118","DOI":"10.1073\/pnas.2006800118","volume":"118","author":"K Petrov","year":"2021","unstructured":"Petrov, K., de Almeida Magalhaes, T. & Salic, A. Mechanism and ultrasensitivity in Hedgehog signaling revealed by Patched1 disease mutations. Proc. Natl Acad. Sci. USA 118, e2006800118 (2021).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR203","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1101\/sqb.2016.81.030866","volume":"81","author":"H Varmus","year":"2016","unstructured":"Varmus, H., Unni, A. M. & Lockwood, W. W.\u00a0How cancer genomics drives cancer biology: does synthetic lethality explain mutually exclusive oncogenic mutations? Cold Spring Harb. Symp. Quant. Biol. 81, 247\u2013255 (2016).","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"929_CR204","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1158\/1541-7786.MCR-18-0327","volume":"17","author":"GP Leung","year":"2019","unstructured":"Leung, G. P. et al. Hyperactivation of MAPK signaling is deleterious to RAS\/RAF-mutant melanoma. Mol. Cancer Res. 17, 199\u2013211 (2019).","journal-title":"Mol. Cancer Res."},{"key":"929_CR205","doi-asserted-by":"publisher","first-page":"1664","DOI":"10.1038\/s41588-021-00967-z","volume":"53","author":"T Ito","year":"2021","unstructured":"Ito, T. et al. Paralog knockout profiling identifies DUSP4 and DUSP6 as a digenic dependence in MAPK pathway-driven cancers. Nat. Genet. 53, 1664\u20131672 (2021).","journal-title":"Nat. Genet."},{"key":"929_CR206","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1158\/2159-8290.CD-23-0216","volume":"14","author":"MH Dias","year":"2024","unstructured":"Dias, M. H. et al. Paradoxical activation of oncogenic signaling as a cancer treatment strategy. Cancer Discov. 14, 1276\u20131301 (2024).","journal-title":"Cancer Discov."},{"key":"929_CR207","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52326-1","volume":"15","author":"J Lilja","year":"2024","unstructured":"Lilja, J. et al. SHANK3 depletion leads to ERK signalling overdose and cell death in KRAS-mutant cancers. Nat. Commun. 15, 8002 (2024).","journal-title":"Nat. Commun."},{"key":"929_CR208","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.1016\/j.ccell.2021.07.003","volume":"39","author":"BKA Seong","year":"2021","unstructured":"Seong, B. K. A. et al. TRIM8 modulates the EWS\/FLI oncoprotein to promote survival in Ewing sarcoma. Cancer Cell 39, 1262\u20131278 (2021).","journal-title":"Cancer Cell"},{"key":"929_CR209","doi-asserted-by":"publisher","first-page":"e55119","DOI":"10.1371\/journal.pone.0055119","volume":"8","author":"AH Shain","year":"2013","unstructured":"Shain, A. H. & Pollack, J. R. The spectrum of SWI\/SNF mutations, ubiquitous in human cancers. PLoS ONE 8, e55119 (2013).","journal-title":"PLoS ONE"},{"key":"929_CR210","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1038\/ng.3746","volume":"49","author":"X Wang","year":"2017","unstructured":"Wang, X. et al. SMARCB1-mediated SWI\/SNF complex function is essential for enhancer regulation. Nat. Genet. 49, 289\u2013295 (2017).","journal-title":"Nat. Genet."},{"key":"929_CR211","doi-asserted-by":"publisher","first-page":"1410","DOI":"10.1038\/s41556-018-0221-1","volume":"20","author":"BC Michel","year":"2018","unstructured":"Michel, B. C. et al. A non-canonical SWI\/SNF complex is a synthetic lethal target in cancers driven by BAF complex perturbation. Nat. Cell Biol. 20, 1410\u20131420 (2018).","journal-title":"Nat. Cell Biol."},{"key":"929_CR212","doi-asserted-by":"publisher","first-page":"442","DOI":"10.1038\/s41586-024-07250-1","volume":"628","author":"S Radko-Juettner","year":"2024","unstructured":"Radko-Juettner, S. et al. Targeting DCAF5 suppresses SMARCB1-mutant cancer by stabilizing SWI\/SNF. Nature 628, 442\u2013449 (2024).","journal-title":"Nature"},{"key":"929_CR213","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.ccr.2010.09.006","volume":"18","author":"BG Wilson","year":"2010","unstructured":"Wilson, B. G. et al. Epigenetic antagonism between polycomb and SWI\/SNF complexes during oncogenic transformation. Cancer Cell 18, 316\u2013328 (2010).","journal-title":"Cancer Cell"},{"key":"929_CR214","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1038\/nm.3799","volume":"21","author":"BG Bitler","year":"2015","unstructured":"Bitler, B. G. et al. Synthetic lethality by targeting EZH2 methyltransferase activity in ARID1A-mutated cancers. Nat. Med. 21, 231\u2013238 (2015).","journal-title":"Nat. Med."},{"key":"929_CR215","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1038\/nm.3947","volume":"21","author":"LM LaFave","year":"2015","unstructured":"LaFave, L. M. et al. Loss of BAP1 function leads to EZH2-dependent transformation. Nat. Med. 21, 1344\u20131349 (2015).","journal-title":"Nat. Med."},{"key":"929_CR216","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1016\/j.molcel.2019.11.021","volume":"77","author":"S Tamburri","year":"2020","unstructured":"Tamburri, S. et al. Histone H2AK119 mono-ubiquitination is essential for polycomb-mediated transcriptional repression. Mol. Cell 77, 840\u2013856 (2020).","journal-title":"Mol. Cell"},{"key":"929_CR217","doi-asserted-by":"publisher","first-page":"3526","DOI":"10.1016\/j.molcel.2021.06.020","volume":"81","author":"E Conway","year":"2021","unstructured":"Conway, E. et al. BAP1 enhances polycomb repression by counteracting widespread H2AK119ub1 deposition and chromatin condensation. Mol. Cell 81, 3526\u20133541 (2021).","journal-title":"Mol. Cell"},{"key":"929_CR218","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1016\/S1470-2045(20)30451-4","volume":"21","author":"M Gounder","year":"2020","unstructured":"Gounder, M. et al. Tazemetostat in advanced epithelioid sarcoma with loss of INI1\/SMARCB1: an international, open-label, phase 2 basket study. Lancet Oncol. 21, 1423\u20131432 (2020).","journal-title":"Lancet Oncol."},{"key":"929_CR219","unstructured":"US National Library of Medicine. A study of tulmimetostat DZR123 (CPI-0209) in patients with advanced solid tumors and lymphomas. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04104776 (2019)."},{"key":"929_CR220","doi-asserted-by":"publisher","first-page":"104086","DOI":"10.1016\/j.critrevonc.2023.104086","volume":"190","author":"D Fanale","year":"2023","unstructured":"Fanale, D. et al. Potential agnostic role of BRCA alterations in patients with several solid tumors: one for all, all for one? Crit. Rev. Oncol. Hematol. 190, 104086 (2023).","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"929_CR221","doi-asserted-by":"publisher","first-page":"5510","DOI":"10.1200\/JCO.2024.42.16_suppl.5510","volume":"42","author":"F Simpkins","year":"2024","unstructured":"Simpkins, F. et al. Combination ATR and PARP Inhibitor (CAPRI): a phase 2 study of ceralasertib plus olaparib in patients with recurrent, platinum-sensitive epithelial ovarian cancer (cohort A). J. Clin. Oncol. 42, 5510\u20135510 (2024).","journal-title":"J. Clin. Oncol."},{"key":"929_CR222","doi-asserted-by":"publisher","first-page":"11525","DOI":"10.1200\/JCO.2024.42.16_suppl.11525","volume":"42","author":"V Avutu","year":"2024","unstructured":"Avutu, V. et al. Phase 1 results of the WEE1 inhibitor, azenosertib, in combination with gemcitabine (gem) in adult and pediatric patients (pts) with relapsed or refractory (R\/R) osteosarcoma. J. Clin. Oncol. 42, 11525\u201311525 (2024).","journal-title":"J. Clin. Oncol."},{"key":"929_CR223","doi-asserted-by":"publisher","first-page":"39653","DOI":"10.1039\/D4RA05497K","volume":"14","author":"M Hu","year":"2024","unstructured":"Hu, M. & Chen, X. A review of the known MTA-cooperative PRMT5 inhibitors. RSC Adv. 14, 39653\u201339691 (2024).","journal-title":"RSC Adv."},{"key":"929_CR224","doi-asserted-by":"publisher","first-page":"3761","DOI":"10.1073\/pnas.1014835108","volume":"108","author":"M Scaltriti","year":"2011","unstructured":"Scaltriti, M. et al. Cyclin E amplification\/overexpression is a mechanism of trastuzumab resistance in HER2+\u2009breast cancer patients. Proc. Natl Acad. Sci. USA 108, 3761\u20133766 (2011).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR225","doi-asserted-by":"publisher","first-page":"5331","DOI":"10.1158\/1538-7445.AM2025-5331","volume":"85","author":"JM Munck","year":"2025","unstructured":"Munck, J. M. et al. Abstract 5331: orthosteric CDK2 kinase inhibitors have a distinctive profile when compared to genetic perturbation of CDK2 in CCNE1-amplified and non-amplified tumor cell lines. Cancer Res. 85, 5331\u20135331 (2025).","journal-title":"Cancer Res."},{"key":"929_CR226","doi-asserted-by":"publisher","first-page":"113849","DOI":"10.1016\/j.ejmech.2021.113849","volume":"226","author":"S Hati","year":"2021","unstructured":"Hati, S. et al. AZD5438-PROTAC: a selective CDK2 degrader that protects against cisplatin- and noise-induced hearing loss. Eur. J. Med. Chem. 226, 113849 (2021).","journal-title":"Eur. J. Med. Chem."},{"key":"929_CR227","doi-asserted-by":"publisher","first-page":"3309","DOI":"10.1158\/1538-7445.AM2024-3309","volume":"84","author":"A Gerson-Gurwitz","year":"2024","unstructured":"Gerson-Gurwitz, A. et al. Abstract 3309: Discovery of potent and selective bivalent CDK2 degraders that demonstrate activity in CCNE1amp driven tumors. Cancer Res. 84, 3309 (2024).","journal-title":"Cancer Res."},{"key":"929_CR228","doi-asserted-by":"publisher","first-page":"567","DOI":"10.1038\/s41589-021-00742-5","volume":"17","author":"L Wang","year":"2021","unstructured":"Wang, L. et al. Discovery of a first-in-class CDK2 selective degrader for AML differentiation therapy. Nat. Chem. Biol. 17, 567\u2013575 (2021).","journal-title":"Nat. Chem. Biol."},{"key":"929_CR229","doi-asserted-by":"publisher","first-page":"5806","DOI":"10.1158\/0008-5472.CAN-21-1784","volume":"81","author":"F Vazquez","year":"2021","unstructured":"Vazquez, F. & Sellers, W. R. Are CRISPR screens providing the next generation of therapeutic targets? Cancer Res. 81, 5806\u20135809 (2021).","journal-title":"Cancer Res."},{"key":"929_CR230","doi-asserted-by":"publisher","first-page":"10155","DOI":"10.1021\/acs.jmedchem.8b01318","volume":"61","author":"JPN Papillon","year":"2018","unstructured":"Papillon, J. P. N. et al. Discovery of orally active inhibitors of Brahma homolog (BRM)\/SMARCA2 ATPase activity for the treatment of Brahma related gene 1 (BRG1)\/SMARCA4-mutant cancers. J. Med. Chem. 61, 10155\u201310172 (2018).","journal-title":"J. Med. Chem."},{"key":"929_CR231","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-33430-6","volume":"13","author":"C Kofink","year":"2022","unstructured":"Kofink, C. et al. A selective and orally bioavailable VHL-recruiting PROTAC achieves SMARCA2 degradation in vivo. Nat. Commun. 13, 5969 (2022).","journal-title":"Nat. Commun."},{"key":"929_CR232","doi-asserted-by":"publisher","first-page":"1155","DOI":"10.1021\/acs.jmedchem.4c01904","volume":"68","author":"L Yang","year":"2025","unstructured":"Yang, L. et al. Discovery of SMD-3236: a potent, highly selective and efficacious SMARCA2 degrader for the treatment of SMARC4-deficient human cancers. J. Med. Chem. 68, 1155\u20131178 (2025).","journal-title":"J. Med. Chem."},{"key":"929_CR233","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1158\/0008-5472.CAN-25-1141","volume":"86","author":"M Hulse","year":"2026","unstructured":"Hulse, M. et al. PRT3789 is a first-in-human SMARCA2-selective degrader that induces synthetic lethality in SMARCA4-mutated cancers. Cancer Res. 86, 213\u2013235 (2026).","journal-title":"Cancer Res."},{"key":"929_CR234","doi-asserted-by":"publisher","first-page":"CT109","DOI":"10.1158\/1538-7445.AM2025-CT109","volume":"85","author":"T Yap","year":"2025","unstructured":"Yap, T. et al. Abstract CT109: A first-in-human phase 1 study of LY4050784, an oral, potent, and selective SMARCA2 inhibitor, in patients with advanced solid tumors with SMARCA4 alterations (Trial in Progress). Cancer Res. 85, CT109\u2013CT109 (2025).","journal-title":"Cancer Res."},{"key":"929_CR235","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1038\/nature18621","volume":"535","author":"Y-NP Chen","year":"2016","unstructured":"Chen, Y.-N. P. et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature 535, 148\u2013152 (2016).","journal-title":"Nature"},{"key":"929_CR236","doi-asserted-by":"publisher","first-page":"1283","DOI":"10.1038\/s41417-024-00747-x","volume":"31","author":"X Wang","year":"2024","unstructured":"Wang, X. et al. Recent progress of CDK4\/6 inhibitors\u2019 current practice in breast cancer. Cancer Gene Ther. 31, 1283\u20131291 (2024).","journal-title":"Cancer Gene Ther."},{"key":"929_CR237","doi-asserted-by":"publisher","first-page":"435","DOI":"10.1016\/S1470-2045(17)30180-8","volume":"18","author":"R Dummer","year":"2017","unstructured":"Dummer, R. et al. Binimetinib versus dacarbazine in patients with advanced NRAS-mutant melanoma (NEMO): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 18, 435\u2013445 (2017).","journal-title":"Lancet Oncol."},{"key":"929_CR238","doi-asserted-by":"publisher","first-page":"555","DOI":"10.1158\/1078-0432.CCR-11-1491","volume":"18","author":"JM Kirkwood","year":"2012","unstructured":"Kirkwood, J. M. et al. Phase II, open-label, randomized trial of the MEK1\/2 inhibitor selumetinib as monotherapy versus temozolomide in patients with advanced melanoma. Clin. Cancer Res. 18, 555\u2013567 (2012).","journal-title":"Clin. Cancer Res."},{"key":"929_CR239","doi-asserted-by":"publisher","first-page":"4178","DOI":"10.1200\/JCO.21.02659","volume":"40","author":"R Dummer","year":"2022","unstructured":"Dummer, R. et al. COLUMBUS 5-year update: a randomized, open-label, phase III trial of encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF V600-mutant melanoma. J. Clin. Oncol. 40, 4178\u20134188 (2022).","journal-title":"J. Clin. Oncol."},{"key":"929_CR240","doi-asserted-by":"publisher","first-page":"4621","DOI":"10.1200\/JCO.22.02322","volume":"41","author":"PA Ascierto","year":"2023","unstructured":"Ascierto, P. A. et al. Contribution of MEK Inhibition to BRAF\/MEK inhibitor combination treatment of BRAF-mutant melanoma: part 2 of the randomized, open-label, phase III COLUMBUS trial. J. Clin. Oncol. 41, 4621\u20134631 (2023).","journal-title":"J. Clin. Oncol."},{"key":"929_CR241","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1056\/NEJMoa1412690","volume":"372","author":"C Robert","year":"2015","unstructured":"Robert, C. et al. Improved overall survival in melanoma with combined dabrafenib and trametinib. N. Engl. J. Med. 372, 30\u201339 (2015).","journal-title":"N. Engl. J. Med."},{"key":"929_CR242","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1056\/NEJMoa1408868","volume":"371","author":"J Larkin","year":"2014","unstructured":"Larkin, J. et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N. Engl. J. Med. 371, 1867\u20131876 (2014).","journal-title":"N. Engl. J. Med."},{"key":"929_CR243","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1016\/j.ccell.2015.09.015","volume":"28","author":"SX Pfister","year":"2015","unstructured":"Pfister, S. X. et al. Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell 28, 557\u2013568 (2015).","journal-title":"Cancer Cell"},{"key":"929_CR244","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13837","volume":"7","author":"CT Williamson","year":"2016","unstructured":"Williamson, C. T. et al. ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. Nat. Commun. 7, 13837 (2016).","journal-title":"Nat. Commun."},{"key":"929_CR245","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1038\/nchembio.573","volume":"7","author":"PM Reaper","year":"2011","unstructured":"Reaper, P. M. et al. Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR. Nat. Chem. Biol. 7, 428\u2013430 (2011).","journal-title":"Nat. Chem. Biol."},{"key":"929_CR246","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1038\/s41586-022-04638-9","volume":"604","author":"D Gallo","year":"2022","unstructured":"Gallo, D. et al. CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition. Nature 604, 749\u2013756 (2022).","journal-title":"Nature"},{"key":"929_CR247","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/s41573-022-00542-z","volume":"21","author":"L Boike","year":"2022","unstructured":"Boike, L., Henning, N. J. & Nomura, D. K. Advances in covalent drug discovery. Nat. Rev. Drug. Discov. 21, 881\u2013898 (2022).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"929_CR248","doi-asserted-by":"publisher","first-page":"1275","DOI":"10.1016\/j.tibtech.2018.06.008","volume":"36","author":"G Drewes","year":"2018","unstructured":"Drewes, G. & Knapp, S. Chemoproteomics and chemical probes for target discovery. Trends Biotechnol. 36, 1275\u20131286 (2018).","journal-title":"Trends Biotechnol."},{"key":"929_CR249","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1021\/acs.accounts.1c00065","volume":"54","author":"JN Spradlin","year":"2021","unstructured":"Spradlin, J. N., Zhang, E. & Nomura, D. K. Reimagining druggability using chemoproteomic platforms. Acc. Chem. Res. 54, 1801\u20131813 (2021).","journal-title":"Acc. Chem. Res."},{"key":"929_CR250","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41589-024-01738-7","volume":"21","author":"Y Zhang","year":"2024","unstructured":"Zhang, Y. et al. An allosteric cyclin E-CDK2 site mapped by paralog hopping with covalent probes. Nat. Chem. Biol. 21, 420\u2013431 (2024).","journal-title":"Nat. Chem. Biol."},{"key":"929_CR251","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-38732-x","volume":"14","author":"EB Faber","year":"2023","unstructured":"Faber, E. B. et al. Development of allosteric and selective CDK2 inhibitors for contraception with negative cooperativity to cyclin binding. Nat. Commun. 14, 3213 (2023).","journal-title":"Nat. Commun."},{"key":"929_CR252","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-16559-0","volume":"11","author":"CI Wells","year":"2020","unstructured":"Wells, C. I. et al. Quantifying CDK inhibitor selectivity in live cells. Nat. Commun. 11, 2743 (2020).","journal-title":"Nat. Commun."},{"key":"929_CR253","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-36238-0","volume":"14","author":"JD Harling","year":"2023","unstructured":"Harling, J. D. & Tinworth, C. P. A two-faced selectivity solution to target SMARCA2 for cancer therapy. Nat. Commun. 14, 515 (2023).","journal-title":"Nat. Commun."},{"key":"929_CR254","doi-asserted-by":"publisher","first-page":"47","DOI":"10.36401\/JIPO-24-22","volume":"8","author":"I House","year":"2025","unstructured":"House, I., Valore-Caplan, M., Maris, E. & Falchook, G. S. Cyclin dependent kinase 2 (CDK2) inhibitors in oncology clinical trials: a review. J. Immunother. Precis. Oncol. 8, 47\u201354 (2025).","journal-title":"J. Immunother. Precis. Oncol."},{"key":"929_CR255","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/S1535-6108(03)00053-9","volume":"3","author":"O Tetsu","year":"2003","unstructured":"Tetsu, O. & McCormick, F. Proliferation of cancer cells despite CDK2 inhibition. Cancer Cell 3, 233\u2013245 (2003).","journal-title":"Cancer Cell"},{"key":"929_CR256","doi-asserted-by":"publisher","first-page":"4299","DOI":"10.1158\/0008-5472.CAN-05-2507","volume":"66","author":"M Payton","year":"2006","unstructured":"Payton, M. et al. Discovery and evaluation of dual CDK1 and CDK2 inhibitors. Cancer Res. 66, 4299\u20134308 (2006).","journal-title":"Cancer Res."},{"key":"929_CR257","doi-asserted-by":"publisher","first-page":"805","DOI":"10.1038\/s41586-023-06835-6","volume":"625","author":"R Schmidt","year":"2024","unstructured":"Schmidt, R. et al. Base-editing mutagenesis maps alleles to tune human T cell functions. Nature 625, 805\u2013812 (2024).","journal-title":"Nature"},{"key":"929_CR258","doi-asserted-by":"publisher","first-page":"1320","DOI":"10.1038\/s41589-023-01428-w","volume":"19","author":"H Li","year":"2023","unstructured":"Li, H. et al. Assigning functionality to cysteines by base editing of cancer dependency genes. Nat. Chem. Biol. 19, 1320\u20131330 (2023).","journal-title":"Nat. Chem. Biol."},{"key":"929_CR259","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/s41586-020-2099-x","volume":"580","author":"K Han","year":"2020","unstructured":"Han, K. et al. CRISPR screens in cancer spheroids identify 3D growth specific vulnerabilities. Nature 580, 136\u2013141 (2020).","journal-title":"Nature"},{"key":"929_CR260","doi-asserted-by":"publisher","first-page":"e2403685121","DOI":"10.1073\/pnas.2403685121","volume":"121","author":"JR Ferrarone","year":"2024","unstructured":"Ferrarone, J. R. et al. Genome-wide CRISPR screens in spheroid culture reveal that the tumor suppressor LKB1 inhibits growth via the PIKFYVE lipid kinase. Proc. Natl Acad. Sci. USA 121, e2403685121 (2024).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR261","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s42003-021-02397-3","volume":"4","author":"MY He","year":"2021","unstructured":"He, M. Y. et al. Three-dimensional CRISPR screening reveals epigenetic interaction with anti-angiogenic therapy. Commun. Biol. 4, 1\u201315 (2021).","journal-title":"Commun. Biol."},{"key":"929_CR262","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.molcel.2020.10.010","volume":"80","author":"N Takahashi","year":"2020","unstructured":"Takahashi, N. et al. 3D culture models with CRISPR screens reveal hyperactive NRF2 as a prerequisite for spheroid formation via regulation of proliferation and ferroptosis. Mol. Cell 80, 828\u2013844 (2020).","journal-title":"Mol. Cell"},{"key":"929_CR263","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1158\/2159-8290.CD-20-1851","volume":"12","author":"S Lin","year":"2022","unstructured":"Lin, S. et al. An in vivo CRISPR screening platform for prioritizing therapeutic targets in AML. Cancer Discov. 12, 432\u2013449 (2022).","journal-title":"Cancer Discov."},{"key":"929_CR264","doi-asserted-by":"publisher","first-page":"6330","DOI":"10.1158\/0008-5472.CAN-17-2043","volume":"77","author":"EH Yau","year":"2017","unstructured":"Yau, E. H. et al. Genome-wide CRISPR screen for essential cell growth mediators in mutant KRAS colorectal cancers. Cancer Res. 77, 6330\u20136339 (2017).","journal-title":"Cancer Res."},{"key":"929_CR265","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1038\/s43018-020-0040-8","volume":"1","author":"CH Hulton","year":"2020","unstructured":"Hulton, C. H. et al. Direct genome editing of patient-derived xenografts using CRISPR\u2013Cas9 enables rapid in vivo functional genomics. Nat. Cancer 1, 359\u2013369 (2020).","journal-title":"Nat. Cancer"},{"key":"929_CR266","doi-asserted-by":"publisher","first-page":"681","DOI":"10.1158\/0008-5472.CAN-21-3908","volume":"82","author":"MC Scheidmann","year":"2022","unstructured":"Scheidmann, M. C. et al. An in vivo CRISPR screen identifies stepwise genetic dependencies of metastatic progression. Cancer Res. 82, 681\u2013694 (2022).","journal-title":"Cancer Res."},{"key":"929_CR267","doi-asserted-by":"publisher","first-page":"8045","DOI":"10.1158\/0008-5472.CAN-10-2352","volume":"70","author":"N Chan","year":"2010","unstructured":"Chan, N. et al. Contextual synthetic lethality of cancer cell kill based on the tumor microenvironment. Cancer Res. 70, 8045\u20138054 (2010).","journal-title":"Cancer Res."},{"key":"929_CR268","doi-asserted-by":"publisher","first-page":"e143765","DOI":"10.1172\/JCI143765","volume":"131","author":"KJ Metcalf","year":"2021","unstructured":"Metcalf, K. J., Alazzeh, A., Werb, Z. & Weaver, V. M. Leveraging microenvironmental synthetic lethalities to treat cancer. J. Clin. Invest. 131, e143765 (2021).","journal-title":"J. Clin. Invest."},{"key":"929_CR269","doi-asserted-by":"publisher","first-page":"e70","DOI":"10.1002\/mog2.70","volume":"3","author":"M Ge","year":"2024","unstructured":"Ge, M., Luo, J., Wu, Y., Shen, G. & Kuang, X. The biological essence of synthetic lethality: Bringing new opportunities for cancer therapy. MedComm Oncol. 3, e70 (2024).","journal-title":"MedComm Oncol."},{"key":"929_CR270","doi-asserted-by":"publisher","first-page":"1494","DOI":"10.1038\/s41590-019-0500-4","volume":"20","author":"G Wang","year":"2019","unstructured":"Wang, G. et al. Multiplexed activation of endogenous genes by CRISPRa elicits potent antitumor immunity. Nat. Immunol. 20, 1494\u20131505 (2019).","journal-title":"Nat. Immunol."},{"key":"929_CR271","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29205-8","volume":"13","author":"J Joung","year":"2022","unstructured":"Joung, J. et al. CRISPR activation screen identifies BCL-2 proteins and B3GNT2 as drivers of cancer resistance to T cell-mediated cytotoxicity. Nat. Commun. 13, 1606 (2022).","journal-title":"Nat. Commun."},{"key":"929_CR272","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1038\/nmeth.1638","volume":"8","author":"X Yang","year":"2011","unstructured":"Yang, X. et al. A public genome-scale lentiviral expression library of human ORFs. Nat. Methods 8, 659\u2013661 (2011).","journal-title":"Nat. Methods"},{"key":"929_CR273","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1016\/j.cell.2018.02.037","volume":"173","author":"LM Sack","year":"2018","unstructured":"Sack, L. M. et al. Profound tissue specificity in proliferation control underlies cancer drivers and aneuploidy patterns. Cell 173, 499\u2013514 (2018).","journal-title":"Cell"},{"key":"929_CR274","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1038\/s41588-024-01971-9","volume":"57","author":"SH Fong","year":"2025","unstructured":"Fong, S. H. et al. A multilineage screen identifies actionable synthetic lethal interactions in human cancers. Nat. Genet. 57, 154\u2013164 (2025).","journal-title":"Nat. Genet."},{"key":"929_CR275","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-56818-6","volume":"16","author":"M Pourmousa","year":"2025","unstructured":"Pourmousa, M. et al. AI-driven discovery of synergistic drug combinations against pancreatic cancer. Nat. Commun. 16, 4020 (2025).","journal-title":"Nat. Commun."},{"key":"929_CR276","doi-asserted-by":"publisher","first-page":"bbae425","DOI":"10.1093\/bib\/bbae425","volume":"25","author":"K Fan","year":"2024","unstructured":"Fan, K. et al. Synthetic lethal connectivity and graph transformer improve synthetic lethality prediction. Brief. Bioinform. 25, bbae425 (2024).","journal-title":"Brief. Bioinform."},{"key":"929_CR277","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14620-6","volume":"11","author":"PC DeWeirdt","year":"2020","unstructured":"DeWeirdt, P. C. et al. Genetic screens in isogenic mammalian cell lines without single cell cloning. Nat. Commun. 11, 752 (2020).","journal-title":"Nat. Commun."},{"key":"929_CR278","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.1016\/j.cell.2024.01.042","volume":"187","author":"M Pacesa","year":"2024","unstructured":"Pacesa, M., Pelea, O. & Jinek, M. Past, present, and future of CRISPR genome editing technologies. Cell 187, 1076\u20131100 (2024).","journal-title":"Cell"},{"key":"929_CR279","doi-asserted-by":"publisher","first-page":"eabm6638","DOI":"10.1126\/sciadv.abm6638","volume":"8","author":"X Feng","year":"2022","unstructured":"Feng, X. et al. Genome-wide CRISPR screens using isogenic cells reveal vulnerabilities conferred by loss of tumor suppressors. Sci. Adv. 8, eabm6638 (2022).","journal-title":"Sci. Adv."},{"key":"929_CR280","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1016\/j.chembiol.2023.06.029","volume":"30","author":"V Dvorak","year":"2023","unstructured":"Dvorak, V. et al. Paralog-dependent isogenic cell assay cascade generates highly selective SLC16A3 inhibitors. Cell Chem. Biol. 30, 953\u2013964 (2023).","journal-title":"Cell Chem. Biol."},{"key":"929_CR281","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-025-01273-7","author":"E Gon\u00e7alves","year":"2025","unstructured":"Gon\u00e7alves, E., Ryan, C. J. & Adams, D. J. Synthetic lethality in cancer drug discovery: challenges and opportunities. Nat. Rev. Drug. Discov. https:\/\/doi.org\/10.1038\/s41573-025-01273-7 (2025).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"929_CR282","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-54771-4","volume":"15","author":"Z Cai","year":"2024","unstructured":"Cai, Z. et al. Synthetic augmentation of cancer cell line multi-omic datasets using unsupervised deep learning. Nat. Commun. 15, 10390 (2024).","journal-title":"Nat. Commun."},{"key":"929_CR283","doi-asserted-by":"publisher","first-page":"1176","DOI":"10.1038\/s43018-024-00789-y","volume":"5","author":"X Shi","year":"2024","unstructured":"Shi, X. et al. Building a translational cancer dependency map for the cancer genome atlas. Nat. Cancer 5, 1176\u20131194 (2024).","journal-title":"Nat. Cancer"},{"key":"929_CR284","doi-asserted-by":"publisher","first-page":"eabh1275","DOI":"10.1126\/sciadv.abh1275","volume":"7","author":"Y-C Chiu","year":"2021","unstructured":"Chiu, Y.-C. et al. Predicting and characterizing a cancer dependency map of tumors with deep learning. Sci. Adv. 7, eabh1275 (2021).","journal-title":"Sci. Adv."},{"key":"929_CR285","doi-asserted-by":"publisher","first-page":"752","DOI":"10.3390\/ph16050752","volume":"16","author":"TM Weiskittel","year":"2023","unstructured":"Weiskittel, T. M. et al. Network biology-inspired machine learning features predict cancer gene targets and reveal target coordinating mechanisms. Pharmaceuticals 16, 752 (2023).","journal-title":"Pharmaceuticals"},{"key":"929_CR286","doi-asserted-by":"publisher","first-page":"2675","DOI":"10.1093\/bioinformatics\/btab137","volume":"37","author":"C-H Lin","year":"2021","unstructured":"Lin, C.-H. & Lichtarge, O. Using interpretable deep learning to model cancer dependencies. Bioinformatics 37, 2675\u20132681 (2021).","journal-title":"Bioinformatics"},{"key":"929_CR287","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52900-7","volume":"15","author":"Y Feng","year":"2024","unstructured":"Feng, Y. et al. Benchmarking machine learning methods for synthetic lethality prediction in cancer. Nat. Commun. 15, 9058 (2024).","journal-title":"Nat. Commun."},{"key":"929_CR288","doi-asserted-by":"publisher","first-page":"522","DOI":"10.1038\/s41588-025-02108-2","volume":"57","author":"S Haider","year":"2025","unstructured":"Haider, S. et al. The transcriptomic architecture of common cancers reflects synthetic lethal interactions. Nat. Genet. 57, 522\u2013529 (2025).","journal-title":"Nat. Genet."},{"key":"929_CR289","doi-asserted-by":"publisher","first-page":"2487","DOI":"10.1016\/j.cell.2021.03.030","volume":"184","author":"JS Lee","year":"2021","unstructured":"Lee, J. S. et al. Synthetic lethality-mediated precision oncology via the tumor transcriptome. Cell 184, 2487\u20132502 (2021).","journal-title":"Cell"},{"key":"929_CR290","doi-asserted-by":"publisher","DOI":"10.1038\/s41540-023-00296-3","volume":"9","author":"N Barrena","year":"2023","unstructured":"Barrena, N., Valc\u00e1rcel, L. V., Olaverri-Mendizabal, D., Apaolaza, I. & Planes, F. J. Synthetic lethality in large-scale integrated metabolic and regulatory network models of human cells. NPJ Syst. Biol. Appl. 9, 32 (2023).","journal-title":"NPJ Syst. Biol. Appl."},{"key":"929_CR291","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-52725-4","volume":"15","author":"LV Valc\u00e1rcel","year":"2024","unstructured":"Valc\u00e1rcel, L. V. et al. An automated network-based tool to search for metabolic vulnerabilities in cancer. Nat. Commun. 15, 8685 (2024).","journal-title":"Nat. Commun."},{"key":"929_CR292","doi-asserted-by":"publisher","first-page":"zcaf029","DOI":"10.1093\/narcan\/zcaf029","volume":"7","author":"P Keyl","year":"2025","unstructured":"Keyl, P. et al. Neural interaction explainable AI predicts drug response across cancers. NAR. Cancer 7, zcaf029 (2025).","journal-title":"NAR. Cancer"},{"key":"929_CR293","doi-asserted-by":"publisher","first-page":"570","DOI":"10.1038\/nature18002","volume":"534","author":"KM Backus","year":"2016","unstructured":"Backus, K. M. et al. Proteome-wide covalent ligand discovery in native biological systems. Nature 534, 570\u2013574 (2016).","journal-title":"Nature"},{"key":"929_CR294","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1016\/j.cell.2017.08.051","volume":"171","author":"L Bar-Peled","year":"2017","unstructured":"Bar-Peled, L. et al. Chemical proteomics identifies druggable vulnerabilities in a genetically defined cancer. Cell 171, 696\u2013709 (2017).","journal-title":"Cell"},{"key":"929_CR295","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1016\/j.chembiol.2024.08.006","volume":"31","author":"MJ Niphakis","year":"2024","unstructured":"Niphakis, M. J. & Cravatt, B. F. Ligand discovery by activity-based protein profiling. Cell Chem. Biol. 31, 1636\u20131651 (2024).","journal-title":"Cell Chem. Biol."},{"key":"929_CR296","doi-asserted-by":"publisher","first-page":"2719","DOI":"10.1073\/pnas.0500016102","volume":"102","author":"E Buck","year":"2005","unstructured":"Buck, E. & Wells, J. A. Disulfide trapping to localize small-molecule agonists and antagonists for a G protein-coupled receptor. Proc. Natl Acad. Sci. USA 102, 2719\u20132724 (2005).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"929_CR297","doi-asserted-by":"publisher","first-page":"2536","DOI":"10.1016\/j.cell.2024.03.027","volume":"187","author":"M Takahashi","year":"2024","unstructured":"Takahashi, M. et al. DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell 187, 2536\u20132556.e30 (2024).","journal-title":"Cell"},{"key":"929_CR298","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2026.01.007","author":"LM van Tienen","year":"2026","unstructured":"van Tienen, L. M. et al. Systematic cysteine scanning identifies a druggable pocket in oncogenic KRAS. Cell Chem. Biol. https:\/\/doi.org\/10.1016\/j.chembiol.2026.01.007 (2026).","journal-title":"Cell Chem. Biol."},{"key":"929_CR299","doi-asserted-by":"publisher","first-page":"8951","DOI":"10.1021\/jacs.9b02822","volume":"141","author":"E Resnick","year":"2019","unstructured":"Resnick, E. et al. Rapid covalent-probe discovery by electrophile-fragment screening. J. Am. Chem. Soc. 141, 8951\u20138968 (2019).","journal-title":"J. Am. Chem. Soc."},{"key":"929_CR300","doi-asserted-by":"publisher","first-page":"1050","DOI":"10.1016\/j.chembiol.2024.05.004","volume":"31","author":"SL Schreiber","year":"2024","unstructured":"Schreiber, S. L. Molecular glues and bifunctional compounds: therapeutic modalities based on induced proximity. Cell Chem. Biol. 31, 1050\u20131063 (2024).","journal-title":"Cell Chem. Biol."},{"key":"929_CR301","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1007\/s10637-024-01461-z","volume":"42","author":"NJ Lakhani","year":"2024","unstructured":"Lakhani, N. J. et al. A phase 1b study of the ERK inhibitor MK-8353 plus pembrolizumab in patients with advanced solid tumors. Invest. N. Drugs 42, 581\u2013589 (2024).","journal-title":"Invest. N. Drugs"},{"key":"929_CR302","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1158\/2767-9764.CRC-24-0036","volume":"4","author":"EI Buchbinder","year":"2024","unstructured":"Buchbinder, E. I. et al. A phase II study of ERK inhibition by ulixertinib (BVD-523) in metastatic uveal melanoma. Cancer Res. Commun. 4, 1321\u20131327 (2024).","journal-title":"Cancer Res. Commun."},{"key":"929_CR303","doi-asserted-by":"publisher","first-page":"e2400103","DOI":"10.1200\/PO.24.00103","volume":"8","author":"KT Vo","year":"2024","unstructured":"Vo, K. T. et al. Phase II study of ulixertinib in children and young adults with tumors harboring activating mitogen-activated protein kinase pathway alterations: APEC1621J of the National Cancer Institute-Children\u2019s Oncology Group pediatric MATCH trial. JCO Precis. Oncol. 8, e2400103 (2024).","journal-title":"JCO Precis. Oncol."},{"key":"929_CR304","unstructured":"US National Library of Medicine. ERK inhibitor JSI-1187 in advanced solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06239623 (2024)."},{"key":"929_CR305","unstructured":"US National Library of Medicine. Study of INCB123667 in subjects with advanced solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05238922 (2025)."},{"key":"929_CR306","doi-asserted-by":"publisher","first-page":"2108","DOI":"10.3390\/cancers12082108","volume":"12","author":"A Owais","year":"2020","unstructured":"Owais, A., Mishra, R. K. & Kiyokawa, H. The HECT E3 ligase E6AP\/UBE3A as a therapeutic target in cancer and neurological disorders. Cancers 12, 2108 (2020).","journal-title":"Cancers"},{"key":"929_CR307","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47586-w","volume":"15","author":"Z Wang","year":"2024","unstructured":"Wang, Z. et al. Structural insights into the functional mechanism of the ubiquitin ligase E6AP. Nat. Commun. 15, 3531 (2024).","journal-title":"Nat. Commun."},{"key":"929_CR308","doi-asserted-by":"publisher","first-page":"433","DOI":"10.1002\/ijc.70197","volume":"158","author":"V Wenger","year":"2026","unstructured":"Wenger, V., Garcia-Manero, G., Zeiser, R. & L\u00fcbbert, M. DNA methyltransferase inhibitors in hematological malignancies and solid tumors. Int. J. Cancer 158, 433\u2013461 (2026).","journal-title":"Int. J. Cancer"},{"key":"929_CR309","doi-asserted-by":"publisher","first-page":"1226","DOI":"10.1093\/neuonc\/noaa074","volume":"22","author":"L Federici","year":"2020","unstructured":"Federici, L. et al. 5-Azacitidine in patients with IDH1\/2-mutant recurrent glioma. Neuro. Oncol. 22, 1226\u20131228 (2020).","journal-title":"Neuro. Oncol."},{"key":"929_CR310","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1093\/neuonc\/noaa207","volume":"23","author":"J-W Park","year":"2021","unstructured":"Park, J.-W. et al. TERT and DNMT1 expression predict sensitivity to decitabine in gliomas. Neuro. Oncol. 23, 76\u201387 (2021).","journal-title":"Neuro. Oncol."},{"key":"929_CR311","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1056\/NEJMoa2214131","volume":"388","author":"NC Turner","year":"2023","unstructured":"Turner, N. C. et al. Capivasertib in hormone receptor-positive advanced breast cancer. N. Engl. J. Med. 388, 2058\u20132070 (2023).","journal-title":"N. Engl. J. Med."},{"key":"929_CR312","doi-asserted-by":"publisher","first-page":"4103","DOI":"10.1200\/JCO.24.00427","volume":"42","author":"A Dilawari","year":"2024","unstructured":"Dilawari, A. et al. US Food and Drug Administration approval summary: capivasertib with fulvestrant for hormone receptor-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer with PIK3CA\/AKT1\/PTEN alterations. J. Clin. Oncol. 42, 4103\u20134113 (2024).","journal-title":"J. Clin. Oncol."},{"key":"929_CR313","unstructured":"US National Library of Medicine. A dose escalation study of SHP2 inhibitor in patients with solid tumors harboring KRAS of EGFR mutations. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05163028 (2023)."},{"key":"929_CR314","unstructured":"US National Library of Medicine. A study to assess the safety and tolerability of CFT8634 in locally advanced or metastatic SMARCB1-perturbed cancers, including synovial sarcoma and SMARCB1-null tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05355753 (2024)."},{"key":"929_CR315","unstructured":"US National Library of Medicine. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04965753 (2025)."},{"key":"929_CR316","doi-asserted-by":"publisher","first-page":"e2697","DOI":"10.1097\/MD.0000000000002697","volume":"95","author":"X Wang","year":"2016","unstructured":"Wang, X., Zhang, Y., Han, Z.-G. & He, K.-Y. Malignancy of cancers and synthetic lethal interactions associated with mutations of cancer driver genes. Medicine 95, e2697 (2016).","journal-title":"Medicine"},{"key":"929_CR317","unstructured":"US National Library of Medicine. FHD-609 in subjects with advanced synovial sarcoma or advanced SMARCB1-loss tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04008797 (2025)."},{"key":"929_CR318","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/S1470-2045(22)00277-7","volume":"23","author":"MG Zauderer","year":"2022","unstructured":"Zauderer, M. G. et al. EZH2 inhibitor tazemetostat in patients with relapsed or refractory, BAP1-inactivated malignant pleural mesothelioma: a multicentre, open-label, phase 2 study. Lancet Oncol. 23, 758\u2013767 (2022).","journal-title":"Lancet Oncol."},{"key":"929_CR319","unstructured":"US National Library of Medicine. A study to investigate the safety, tolerability, pharmacokinetics (PK), and preliminary anticancer activity of GSK4524101 alone or with niraparib in participants with solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06077877 (2025)."},{"key":"929_CR320","unstructured":"US National Library of Medicine. Studying the safety and determining the optimal dose of novobiocin in patients with tumors that have alterations in DNA repair genes. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05687110 (2025)."},{"key":"929_CR321","unstructured":"US National Library of Medicine. Study of SYN818 for the treatment of advanced or metastatic solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06666270 (2025)."},{"key":"929_CR322","unstructured":"US National Library of Medicine. Study of orally administered MOMA-313 in participants with advanced or metastatic solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06545942 (2025)."},{"key":"929_CR323","unstructured":"US National Library of Medicine. Study of ART6043 in advanced\/metastatic solid tumors patients. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05898399 (2024)."},{"key":"929_CR324","doi-asserted-by":"publisher","first-page":"108865","DOI":"10.1016\/j.pharmthera.2025.108865","volume":"271","author":"C Torrado","year":"2025","unstructured":"Torrado, C., Ashton, N. W., D\u2019Andrea, A. D. & Yap, T. A. USP1 inhibition: a journey from target discovery to clinical translation. Pharmacol. Ther. 271, 108865 (2025).","journal-title":"Pharmacol. Ther."},{"key":"929_CR325","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1056\/NEJMoa1706450","volume":"377","author":"M Robson","year":"2017","unstructured":"Robson, M. et al. Olaparib for metastatic breast cancer in patients with a germline BRCA mutation. N. Engl. J. Med. 377, 523\u2013533 (2017).","journal-title":"N. Engl. J. Med."},{"key":"929_CR326","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1056\/NEJMoa1810858","volume":"379","author":"K Moore","year":"2018","unstructured":"Moore, K. et al. Maintenance olaparib in patients with newly diagnosed advanced ovarian cancer. N. Engl. J. Med. 379, 2495\u20132505 (2018).","journal-title":"N. Engl. J. Med."},{"key":"929_CR327","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1056\/NEJMoa1903387","volume":"381","author":"T Golan","year":"2019","unstructured":"Golan, T. et al. Maintenance olaparib for germline BRCA-mutated metastatic pancreatic cancer. N. Engl. J. Med. 381, 317\u2013327 (2019).","journal-title":"N. Engl. J. Med."},{"key":"929_CR328","doi-asserted-by":"publisher","first-page":"2091","DOI":"10.1056\/NEJMoa1911440","volume":"382","author":"J de Bono","year":"2020","unstructured":"de Bono, J. et al. Olaparib for metastatic castration-resistant prostate cancer. N. Engl. J. Med. 382, 2091\u20132102 (2020).","journal-title":"N. Engl. J. Med."},{"key":"929_CR329","doi-asserted-by":"publisher","first-page":"116130","DOI":"10.1016\/j.biopha.2024.116130","volume":"171","author":"P Gou","year":"2024","unstructured":"Gou, P. & Zhang, W. Protein lysine acetyltransferase CBP\/p300: a promising target for small molecules in cancer treatment. Biomed. Pharmacother. 171, 116130 (2024).","journal-title":"Biomed. Pharmacother."},{"key":"929_CR330","unstructured":"US National Library of Medicine. A study to assess the safety, tolerability, and efficacy of NDI-219216 in patients with advanced solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06898450 (2025)."},{"key":"929_CR331","unstructured":"US National Library of Medicine. A study to investigate the safety, pharmacokinetics, and preliminary effectiveness of GSK4418959 alone or in combination with other anti-cancer agents in participants with solid tumors (SYLVER). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06710847 (2025)."},{"key":"929_CR332","unstructured":"US National Library of Medicine. A study to evaluate the safety, pharmacokinetics, and anti-tumor activity of VVD-133214 as monotherapy and in combination with pembrolizumab in participants with advanced solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06004245 (2025)."},{"key":"929_CR333","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.1158\/1078-0432.CCR-20-5032","volume":"27","author":"D Casey","year":"2021","unstructured":"Casey, D. et al. FDA approval summary: selumetinib for plexiform neurofibroma. Clin. Cancer Res. 27, 4142\u20134146 (2021).","journal-title":"Clin. Cancer Res."},{"key":"929_CR334","doi-asserted-by":"publisher","first-page":"e18330","DOI":"10.1111\/jcmm.18330","volume":"28","author":"KA Papavassiliou","year":"2024","unstructured":"Papavassiliou, K. A., Sofianidi, A. A. & Papavassiliou, A. G. YAP\/TAZ\u2013TEAD signalling axis: a new therapeutic target in malignant pleural mesothelioma. J. Cell. Mol. Med. 28, e18330 (2024).","journal-title":"J. Cell. Mol. Med."},{"key":"929_CR335","unstructured":"US National Library of Medicine. A study of ION537 in patients with molecularly selected advanced solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04659096 (2022)."},{"key":"929_CR336","unstructured":"US National Library of Medicine. Study to evaluate VT3989 in patients with metastatic solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04665206 (2025)."},{"key":"929_CR337","doi-asserted-by":"publisher","first-page":"2289","DOI":"10.1158\/1078-0432.CCR-12-1956","volume":"19","author":"M Axelson","year":"2013","unstructured":"Axelson, M. et al. U.S. Food and Drug Administration approval: vismodegib for recurrent, locally advanced, or metastatic basal cell carcinoma. Clin. Cancer Res. 19, 2289\u20132293 (2013).","journal-title":"Clin. Cancer Res."},{"key":"929_CR338","doi-asserted-by":"publisher","first-page":"2377","DOI":"10.1158\/1078-0432.CCR-16-2051","volume":"23","author":"D Casey","year":"2017","unstructured":"Casey, D. et al. FDA approval summary: sonidegib for locally advanced basal cell carcinoma. Clin. Cancer Res. 23, 2377\u20132381 (2017).","journal-title":"Clin. Cancer Res."},{"key":"929_CR339","doi-asserted-by":"publisher","first-page":"1326","DOI":"10.1101\/gad.191056.112","volume":"26","author":"M Xiao","year":"2012","unstructured":"Xiao, M. et al. Inhibition of \u03b1-KG-dependent histone and DNA demethylases by fumarate and succinate that are accumulated in mutations of FH and SDH tumor suppressors. Genes. Dev. 26, 1326\u20131338 (2012).","journal-title":"Genes. Dev."},{"key":"929_CR340","unstructured":"US National Library of Medicine. A study of PRT7732, an oral SMARCA2 degrader, in patients with advanced or metastatic solid tumors with a SMARCA4 mutation. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06560645 (2025)."},{"key":"929_CR341","unstructured":"US National Library of Medicine. A study of LY4050784 in participants with advanced or metastatic solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06561685 (2025)."},{"key":"929_CR342","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1007\/s40265-020-01288-x","volume":"80","author":"SM Hoy","year":"2020","unstructured":"Hoy, S. M. Tazemetostat: first approval. Drugs 80, 513\u2013521 (2020).","journal-title":"Drugs"},{"key":"929_CR343","doi-asserted-by":"publisher","first-page":"2064","DOI":"10.1158\/1078-0432.CCR-18-3133","volume":"25","author":"MM Gounder","year":"2019","unstructured":"Gounder, M. M. et al. Immunologic correlates of the abscopal effect in a SMARCB1\/INI1-negative poorly differentiated chordoma after EZH2 inhibition and radiotherapy. Clin. Cancer Res. 25, 2064\u20132071 (2019).","journal-title":"Clin. Cancer Res."},{"key":"929_CR344","doi-asserted-by":"publisher","first-page":"1355","DOI":"10.1093\/jnci\/djad085","volume":"115","author":"SN Chi","year":"2023","unstructured":"Chi, S. N. et al. Tazemetostat for tumors harboring SMARCB1\/SMARCA4 or EZH2 alterations: results from NCI-COG pediatric MATCH APEC1621C. J. Natl. Cancer Inst. 115, 1355\u20131363 (2023).","journal-title":"J. Natl. Cancer Inst."},{"key":"929_CR345","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.ejca.2011.11.027","volume":"48","author":"E Calvo","year":"2012","unstructured":"Calvo, E. et al. Everolimus in metastatic renal cell carcinoma: subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study. Eur. J. Cancer 48, 333\u2013339 (2012).","journal-title":"Eur. J. Cancer"},{"key":"929_CR346","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/S0140-6736(12)61134-9","volume":"381","author":"DN Franz","year":"2013","unstructured":"Franz, D. N. et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet 381, 125\u2013132 (2013).","journal-title":"Lancet"},{"key":"929_CR347","doi-asserted-by":"publisher","first-page":"5003","DOI":"10.1158\/1078-0432.CCR-24-1199","volume":"30","author":"J Fallah","year":"2024","unstructured":"Fallah, J. et al. FDA approval summary: belzutifan for patients with advanced renal cell carcinoma. Clin. Cancer Res. 30, 5003\u20135008 (2024).","journal-title":"Clin. Cancer Res."},{"key":"929_CR348","unstructured":"US National Library of Medicine. Study of IDE397 in participants with solid tumors harboring MTAP deletion. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT04794699 (2024)."},{"key":"929_CR349","unstructured":"US National Library of Medicine. S095035 as a single agent and in combination in adult participants with advanced or metastatic solid tumors with deletion of MTAP. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06188702 (2025)."},{"key":"929_CR350","unstructured":"US National Library of Medicine. Study of ISM3412 in participants with locally advanced\/metastatic solid tumors. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06414460 (2025)."},{"key":"929_CR351","doi-asserted-by":"publisher","first-page":"TPS3167","DOI":"10.1200\/JCO.2022.40.16_suppl.TPS3167","volume":"40","author":"MA Villalona-Calero","year":"2022","unstructured":"Villalona-Calero, M. A. et al. Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors. J. Clin. Oncol. 40, TPS3167\u2013TPS3167 (2022).","journal-title":"J. Clin. Oncol."},{"key":"929_CR352","unstructured":"US National Library of Medicine. A study of AZD3470, a PRMT5 inhibitor, in patients with MTAP deficient advanced\/metastatic solid tumors (PRIMROSE). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06130553 (2025)."},{"key":"929_CR353","unstructured":"US National Library of Medicine. Phase 1 study of MRTX1719 in solid tumors with MTAP deletion. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05245500 (2025)."},{"key":"929_CR354","unstructured":"US National Library of Medicine. AZD3470 as monotherapy and in combination with anticancer agents in participants with relapsed\/refractory haematologic malignancies. (PRIMAVERA). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06137144 (2025)."},{"key":"929_CR355","unstructured":"US National Library of Medicine. A phase 2 study of AMG 193 in participants with MTAP-deleted advanced NSCLC (MTAPESTRY 201). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06593522 (2025)."},{"key":"929_CR356","unstructured":"US National Library of Medicine. AMG 193 alone or in combination with other therapies in subjects with advanced thoracic tumors with homozygous MTAP-deletion (Master Protocol) (MTAPESTRY 104). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06333951 (2025)."},{"key":"929_CR357","unstructured":"US National Library of Medicine. A study evaluating AMG 193 in combination with other therapies in participants with advanced gastrointestinal, biliary tract, or pancreatic cancers with homozygous methylthioadenosine phosphorylase (MTAP)-deletion (MTAPESTRY 103) (MTAPESTRY 103). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06360354 (2025)."},{"key":"929_CR358","unstructured":"US National Library of Medicine. Clinical trial of BMS-986504 in recurrent GBM patients. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06883747 (2025)."},{"key":"929_CR359","unstructured":"US National Library of Medicine. A study of BMS-986504 in participants with pre-treated advanced or metastatic non-small cell lung cancer (NSCLC) with homozygous MTAP deletion (MountainTAP-9). Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT06855771 (2025)."},{"key":"929_CR360","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-35378-z","volume":"13","author":"S Srivatsa","year":"2022","unstructured":"Srivatsa, S. et al. Discovery of synthetic lethal interactions from large-scale pan-cancer perturbation screens. Nat. Commun. 13, 7748 (2022).","journal-title":"Nat. Commun."},{"key":"929_CR361","doi-asserted-by":"publisher","first-page":"2300","DOI":"10.1158\/2159-8290.CD-20-1542","volume":"11","author":"Z Yang","year":"2021","unstructured":"Yang, Z. et al. Transcriptional silencing of ALDH2 confers a dependency on Fanconi anemia proteins in acute myeloid leukemia. Cancer Discov. 11, 2300\u20132315 (2021).","journal-title":"Cancer Discov."},{"key":"929_CR362","doi-asserted-by":"publisher","first-page":"565","DOI":"10.3892\/mco.2013.99","volume":"1","author":"JL Hays","year":"2013","unstructured":"Hays, J. L. et al. A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety. Mol. Clin. Oncol. 1, 565\u2013569 (2013).","journal-title":"Mol. Clin. Oncol."},{"key":"929_CR363","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1097\/MPA.0000000000000394","volume":"44","author":"J-B Bachet","year":"2015","unstructured":"Bachet, J.-B. et al. Asparagine synthetase expression and phase I study with L-asparaginase encapsulated in red blood cells in patients with pancreatic adenocarcinoma. Pancreas 44, 1141\u20131147 (2015).","journal-title":"Pancreas"},{"key":"929_CR364","doi-asserted-by":"publisher","first-page":"1778","DOI":"10.1200\/JCO.2016.71.3230","volume":"35","author":"E Beddowes","year":"2017","unstructured":"Beddowes, E. et al. Phase 1 dose-escalation study of pegylated arginine deiminase, cisplatin, and pemetrexed in patients with argininosuccinate synthetase 1-deficient thoracic cancers. J. Clin. Oncol. 35, 1778\u20131785 (2017).","journal-title":"J. Clin. Oncol."},{"key":"929_CR365","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1001\/jamaoncol.2016.3049","volume":"3","author":"PW Szlosarek","year":"2017","unstructured":"Szlosarek, P. W. et al. Arginine deprivation with pegylated arginine deiminase in patients with argininosuccinate synthetase 1-deficient malignant pleural mesothelioma: a randomized clinical trial. JAMA Oncol. 3, 58\u201366 (2017).","journal-title":"JAMA Oncol."},{"key":"929_CR366","doi-asserted-by":"publisher","first-page":"1533","DOI":"10.1038\/s41416-020-01230-8","volume":"124","author":"S Yao","year":"2021","unstructured":"Yao, S. et al. Phase 1 trial of ADI-PEG20 plus cisplatin in patients with pretreated metastatic melanoma or other advanced solid malignancies. Br. J. Cancer 124, 1533\u20131539 (2021).","journal-title":"Br. J. Cancer"},{"key":"929_CR367","doi-asserted-by":"publisher","first-page":"935553","DOI":"10.3389\/fphar.2022.935553","volume":"13","author":"N Sun","year":"2022","unstructured":"Sun, N. & Zhao, X. Argininosuccinate synthase 1, arginine deprivation therapy and cancer management. Front. Pharmacol. 13, 935553 (2022).","journal-title":"Front. Pharmacol."},{"key":"929_CR368","unstructured":"US National Library of Medicine. Ph 1 study of ADI PEG 20 in pediatric subjects who are argininosuccinate synthetase (ASS) deficient. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT01528384 (2014)."},{"key":"929_CR369","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-025-01917-w","volume":"17","author":"L Nougarede","year":"2025","unstructured":"Nougarede, L., Hazane-Puch, F., de Fraipont, F., Jacquet, E. & Bidart, M. BRCA1 promoter methylation predicts PARPi response in ovarian cancer: insights from the KOMET study. Clin. Epigenetics 17, 140 (2025).","journal-title":"Clin. Epigenetics"},{"key":"929_CR370","unstructured":"US National Library of Medicine. A phase I\/II study of VLS-1488 in subjects with advanced cancer. Clinicaltrials.gov https:\/\/clinicaltrials.gov\/study\/NCT05902988 (2025)."},{"key":"929_CR371","doi-asserted-by":"publisher","first-page":"102650","DOI":"10.1016\/j.ctrv.2023.102650","volume":"121","author":"L Incorvaia","year":"2023","unstructured":"Incorvaia, L. et al. Theranostic biomarkers and PARP-inhibitors effectiveness in patients with non-BRCA associated homologous recombination deficient tumors: still looking through a dirty glass window? Cancer Treat. Rev. 121, 102650 (2023).","journal-title":"Cancer Treat. Rev."},{"key":"929_CR372","doi-asserted-by":"publisher","first-page":"2500","DOI":"10.1056\/NEJMc1713444","volume":"377","author":"M Yarchoan","year":"2017","unstructured":"Yarchoan, M., Hopkins, A. & Jaffee, E. M. Tumor mutational burden and response rate to PD-1 inhibition. N. Engl. J. Med. 377, 2500\u20132501 (2017).","journal-title":"N. Engl. J. Med."},{"key":"929_CR373","doi-asserted-by":"publisher","first-page":"1160","DOI":"10.1001\/jamaoncol.2022.1981","volume":"8","author":"B Ricciuti","year":"2022","unstructured":"Ricciuti, B. et al. Association of high tumor mutation burden in non-small cell lung cancers with increased immune infiltration and improved clinical outcomes of PD-L1 blockade across PD-L1 expression levels. JAMA Oncol. 8, 1160\u20131168 (2022).","journal-title":"JAMA Oncol."},{"key":"929_CR374","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1038\/s41392-023-01522-4","volume":"8","author":"Q Sun","year":"2023","unstructured":"Sun, Q. et al. Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends. Signal. Transduct. Target. Ther. 8, 320 (2023).","journal-title":"Signal. Transduct. Target. Ther."},{"key":"929_CR375","doi-asserted-by":"publisher","first-page":"1383456","DOI":"10.3389\/fimmu.2024.1383456","volume":"15","author":"SA Javed","year":"2024","unstructured":"Javed, S. A., Najmi, A., Ahsan, W. & Zoghebi, K. Targeting PD-1\/PD-L-1 immune checkpoint inhibition for cancer immunotherapy: success and challenges. Front. Immunol. 15, 1383456 (2024).","journal-title":"Front. Immunol."},{"key":"929_CR376","doi-asserted-by":"publisher","unstructured":"Chang, L., Shaw, K. L., Vazquez, F. & Sellers, W. R. Figure 2 specific data from DepMap 24Q4 data release. Figshare https:\/\/doi.org\/10.6084\/m9.figshare.31872121 (2026).","DOI":"10.6084\/m9.figshare.31872121"}],"container-title":["Nature Reviews Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41568-026-00929-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41568-026-00929-9","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41568-026-00929-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T12:04:30Z","timestamp":1782734670000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41568-026-00929-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,23]]},"references-count":376,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["929"],"URL":"https:\/\/doi.org\/10.1038\/s41568-026-00929-9","relation":{},"ISSN":["1474-175X","1474-1768"],"issn-type":[{"value":"1474-175X","type":"print"},{"value":"1474-1768","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,23]]},"assertion":[{"value":"18 March 2026","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 April 2026","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"L.C. is an employee of Aditum Bio. F.V. receives research support from the Dependency Map Consortium, Riva Therapeutics, Bristol-Myers Squibb, Merck, Illumina and Deerfield Management; is on the scientific advisory board of GSK; is a consultant and holds equity in Riva Therapeutics; and is a cofounder and holds equity in Jumble Therapeutics. W.R.S. is a board or scientific advisory board member and\/or holds equity in Atavistik Bio, CJ Bioscience, Delphia Therapeutics, Ideaya Biosciences, Pierre Fabre, RedRidge Bio and Scorpion Therapeutics, has consulted for Array, Astex, Epidarex Capital, Ipsen, Merck Pharmaceuticals, Sanofi and Servier and receives or received research funding from Bayer Pharmaceutical, Bristol-Myers Squibb, Boehringer-Ingelheim, Ideaya Biosciences, Calico Biosciences, Novartis Pharmaceuticals and Servier Pharmaceuticals. W.R.S. is a co-patent holder on\n                      EGFR\n                      mutation diagnostic patents. K.S. declares no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}