{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T09:08:44Z","timestamp":1792487324180,"version":"4.5.0"},"reference-count":44,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T00:00:00Z","timestamp":1767398400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":32,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"funder":[{"DOI":"10.13039\/100000982","name":"Conquer Cancer Foundation","doi-asserted-by":"publisher","award":["707457"],"award-info":[{"award-number":["707457"]}],"id":[{"id":"10.13039\/100000982","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["197819"],"award-info":[{"award-number":["197819"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Gouvernement du Canada | Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["180379"],"award-info":[{"award-number":["180379"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000196","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","award":["42153"],"award-info":[{"award-number":["42153"]}],"id":[{"id":"10.13039\/501100000196","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"DOI":"10.1038\/s41467-025-68076-7","type":"journal-article","created":{"date-parts":[[2026,1,4]],"date-time":"2026-01-04T02:20:27Z","timestamp":1767493227000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Binimetinib and encorafenib for the treatment of advanced solid tumors with non-V600E BRAF mutations: results from the Phase II BEAVER trial"],"prefix":"10.1038","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9845-4603","authenticated-orcid":false,"given":"April A. N.","family":"Rose","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3433-6520","authenticated-orcid":false,"given":"Jennifer","family":"Maxwell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8831-7871","authenticated-orcid":false,"given":"Emmanuelle","family":"Rousselle","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7425-8345","authenticated-orcid":false,"given":"Chantel L.","family":"Mukonoweshuro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8019-2481","authenticated-orcid":false,"given":"Islam E.","family":"Elkholi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melody","family":"Riaud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Biondini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Cianfarano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Soria-Bretones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chantal","family":"Tobin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"McGuire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhoda W. Y.","family":"Law","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Elia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben X.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"King","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor J.","family":"Pugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaid Saeed","family":"Kamil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9840-7057","authenticated-orcid":false,"given":"Marcus","family":"Butler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances A.","family":"Shepherd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3249-4602","authenticated-orcid":false,"given":"Natasha B.","family":"Leighl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albiruni Abdul","family":"Razak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2363-8707","authenticated-orcid":false,"given":"Aaron","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel D.","family":"Saibil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-2999","authenticated-orcid":false,"given":"Philippe L.","family":"Bedard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5568-6586","authenticated-orcid":false,"given":"Peter M.","family":"Siegel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3500-0540","authenticated-orcid":false,"given":"Lillian L.","family":"Siu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1080-0998","authenticated-orcid":false,"given":"David W.","family":"Cescon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-3042","authenticated-orcid":false,"given":"Anna","family":"Spreafico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,3]]},"reference":[{"key":"68076_CR1","doi-asserted-by":"publisher","first-page":"3183","DOI":"10.1038\/s41388-018-0171-x","volume":"37","author":"M Dankner","year":"2018","unstructured":"Dankner, M., Rose, A. A. N., Rajkumar, S., Siegel, P. M. & Watson, I. R. Classifying BRAF alterations in cancer: new rational therapeutic strategies for actionable mutations. Oncogene 37, 3183\u20133199 (2018).","journal-title":"Oncogene"},{"key":"68076_CR2","doi-asserted-by":"publisher","first-page":"e154943","DOI":"10.1172\/JCI154943","volume":"132","author":"MR Waarts","year":"2022","unstructured":"Waarts, M. R., Stonestrom, A. J., Park, Y. C. & Levine, R. L. Targeting mutations in cancer.  J. Clin. Investig. 132, e154943 (2022).","journal-title":"J. Clin. Investig."},{"key":"68076_CR3","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1038\/s41591-023-02321-8","volume":"29","author":"V Subbiah","year":"2023","unstructured":"Subbiah, V. et al. Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. Nat. Med. 29, 1103\u20131112 (2023).","journal-title":"Nat. Med."},{"key":"68076_CR4","doi-asserted-by":"publisher","first-page":"445","DOI":"10.3390\/cancers16020445","volume":"16","author":"S Kazandjian","year":"2024","unstructured":"Kazandjian, S. et al. The clinical, genomic, and transcriptomic landscape of BRAF mutant cancers.  Cancers 16, 445 (2024).","journal-title":"Cancers"},{"key":"68076_CR5","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.ccell.2015.08.001","volume":"28","author":"Z Yao","year":"2015","unstructured":"Yao, Z. et al. BRAF mutants evade ERK-dependent feedback by different mechanisms that determine their sensitivity to pharmacologic inhibition. Cancer Cell 28, 370\u2013383 (2015).","journal-title":"Cancer Cell"},{"key":"68076_CR6","doi-asserted-by":"publisher","first-page":"234","DOI":"10.1038\/nature23291","volume":"548","author":"Z Yao","year":"2017","unstructured":"Yao, Z. et al. Tumours with class 3 BRAF mutants are sensitive to the inhibition of activated RAS. Nature 548, 234\u2013238 (2017).","journal-title":"Nature"},{"key":"68076_CR7","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1038\/s41556-018-0169-1","volume":"20","author":"RJ Nichols","year":"2018","unstructured":"Nichols, R. J. et al. RAS nucleotide cycling underlies the SHP2 phosphatase dependence of mutant BRAF-, NF1- and RAS-driven cancers. Nat. Cell Biol. 20, 1064\u20131073 (2018).","journal-title":"Nat. Cell Biol."},{"key":"68076_CR8","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.celrep.2018.12.013","volume":"26","author":"TA Ahmed","year":"2019","unstructured":"Ahmed, T. A. et al. SHP2 drives adaptive resistance to ERK signaling inhibition in molecularly defined subsets of ERK-dependent tumors. Cell Rep. 26, 65\u201378.e65 (2019).","journal-title":"Cell Rep."},{"key":"68076_CR9","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/sj.cr.7290105","volume":"12","author":"W Zhang","year":"2002","unstructured":"Zhang, W. & Liu, H. T. MAPK signal pathways in the regulation of cell proliferation in mammalian cells. Cell Res. 12, 9\u201318 (2002).","journal-title":"Cell Res."},{"key":"68076_CR10","doi-asserted-by":"publisher","first-page":"758","DOI":"10.1016\/j.molcel.2019.03.020","volume":"74","author":"BR Topacio","year":"2019","unstructured":"Topacio, B. R. et al. Cyclin D-Cdk4,6 drives cell-cycle progression via the retinoblastoma protein\u2019s C-terminal helix. Mol. Cell 74, 758\u2013770.e754 (2019).","journal-title":"Mol. Cell"},{"key":"68076_CR11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1091\/mbc.6.4.387","volume":"6","author":"JW Harper","year":"1995","unstructured":"Harper, J. W. et al. Inhibition of cyclin-dependent kinases by p21. Mol. Biol. Cell 6, 387\u2013400 (1995).","journal-title":"Mol. Biol. Cell"},{"key":"68076_CR12","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1038\/nature08833","volume":"464","author":"G Hatzivassiliou","year":"2010","unstructured":"Hatzivassiliou, G. et al. RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth. Nature 464, 431\u2013435 (2010).","journal-title":"Nature"},{"key":"68076_CR13","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1158\/2159-8290.CD-12-0097","volume":"2","author":"KB Dahlman","year":"2012","unstructured":"Dahlman, K. B. et al. BRAFL597 mutations in melanoma are associated with sensitivity to MEK inhibitors. Cancer Discov. 2, 791\u2013797 (2012).","journal-title":"Cancer Discov."},{"key":"68076_CR14","doi-asserted-by":"publisher","first-page":"1812","DOI":"10.1158\/1078-0432.CCR-19-3443","volume":"26","author":"DB Johnson","year":"2020","unstructured":"Johnson, D. B. et al. Trametinib activity in patients with solid tumors and lymphomas harboring BRAF non-V600 mutations or fusions: results from NCI-MATCH (EAY131). Clin. Cancer Res. 26, 1812\u20131819 (2020).","journal-title":"Clin. Cancer Res."},{"key":"68076_CR15","doi-asserted-by":"publisher","first-page":"6483","DOI":"10.1158\/1078-0432.CCR-17-3384","volume":"24","author":"M Dankner","year":"2018","unstructured":"Dankner, M. et al. Dual MAPK inhibition is an effective therapeutic strategy for a subset of class II BRAF mutant melanomas. Clin. Cancer Res. 24, 6483\u20136494 (2018).","journal-title":"Clin. Cancer Res."},{"key":"68076_CR16","doi-asserted-by":"publisher","first-page":"110634","DOI":"10.1016\/j.celrep.2022.110634","volume":"39","author":"S Rajkumar","year":"2022","unstructured":"Rajkumar, S. et al. Melanomas with concurrent BRAF non-p.V600 and NF1 loss-of-function mutations are targetable by BRAF\/MEK inhibitor combination therapy. Cell Rep. 39, 110634 (2022).","journal-title":"Cell Rep."},{"key":"68076_CR17","unstructured":"Dankner, M. et al. Clinical activity of mitogen-activated protein kinase\u2013targeted therapies in patients with non\u2013V600 BRAF-mutant tumors. JCO Precis. Oncol. 6, e2200107 (2022)."},{"key":"68076_CR18","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/S1470-2045(18)30142-6","volume":"19","author":"R Dummer","year":"2018","unstructured":"Dummer, R. et al. Encorafenib plus binimetinib versus vemurafenib or encorafenib in patients with BRAF-mutant melanoma (COLUMBUS): a multicentre, open-label, randomised phase 3 trial.  Lancet Oncol. 19, 603\u2013615 (2018).","journal-title":"Lancet Oncol."},{"key":"68076_CR19","doi-asserted-by":"publisher","first-page":"3700","DOI":"10.1200\/JCO.23.00774","volume":"41","author":"GJ Riely","year":"2023","unstructured":"Riely, G. J. et al. Phase II, open-label study of encorafenib plus binimetinib in patients with BRAFV600-mutant metastatic non\u2013small-cell lung cancer. J. Clin. Oncol. 41, 3700\u20133711 (2023).","journal-title":"J. Clin. Oncol."},{"key":"68076_CR20","doi-asserted-by":"publisher","first-page":"80","DOI":"10.1158\/2159-8290.CD-13-0642","volume":"4","author":"H Shi","year":"2014","unstructured":"Shi, H. et al. Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy. Cancer Discov. 4, 80\u201393 (2014).","journal-title":"Cancer Discov."},{"key":"68076_CR21","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.ccell.2014.11.018","volume":"27","author":"G Moriceau","year":"2015","unstructured":"Moriceau, G. et al. Tunable-combinatorial mechanisms of acquired resistance limit the efficacy of BRAF\/MEK cotargeting but result in melanoma drug addiction. Cancer Cell 27, 240\u2013256 (2015).","journal-title":"Cancer Cell"},{"key":"68076_CR22","doi-asserted-by":"publisher","first-page":"6513","DOI":"10.1158\/0008-5472.CAN-17-0768","volume":"77","author":"R Yaeger","year":"2017","unstructured":"Yaeger, R. et al. Mechanisms of acquired resistance to BRAF V600E inhibition in colon cancers converge on RAF dimerization and are sensitive to its inhibition. Cancer Res. 77, 6513\u20136523 (2017).","journal-title":"Cancer Res."},{"key":"68076_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-018-0051-4","volume":"2","author":"M-C Wagle","year":"2018","unstructured":"Wagle, M.-C. et al. A transcriptional MAPK pathway activity score (MPAS) is a clinically relevant biomarker in multiple cancer types. npj Precis. Oncol. 2, 7 (2018).","journal-title":"npj Precis. Oncol."},{"key":"68076_CR24","doi-asserted-by":"publisher","first-page":"1779","DOI":"10.1038\/ng.3984","volume":"49","author":"RM Meyers","year":"2017","unstructured":"Meyers, R. M. et al. Computational correction of copy number effect improves specificity of CRISPR\u2013Cas9 essentiality screens in cancer cells. Nat. Genet. 49, 1779\u20131784 (2017).","journal-title":"Nat. Genet."},{"key":"68076_CR25","doi-asserted-by":"crossref","unstructured":"Dempster, J. M. et al. Extracting biological insights from the Project Achilles genome-scale CRISPR screens in cancer cell lines. Preprint at https:\/\/www.biorxiv.org\/content\/10.1101\/720243v1 (2019).","DOI":"10.1101\/720243"},{"key":"68076_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/srep27454","volume":"6","author":"M Atefi","year":"2016","unstructured":"Atefi, M. et al. CRAF R391W is a melanoma driver oncogene. Sci. Rep. 6, 27454 (2016).","journal-title":"Sci. Rep."},{"key":"68076_CR27","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1038\/s41568-023-00650-x","volume":"24","author":"M Riaud","year":"2024","unstructured":"Riaud, M. et al. The role of CRAF in cancer progression: from molecular mechanisms to precision therapies. Nat. Rev. Cancer 24, 105\u2013122 (2024).","journal-title":"Nat. Rev. Cancer"},{"key":"68076_CR28","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1158\/2159-8290.CD-17-1452","volume":"8","author":"Y Gao","year":"2018","unstructured":"Gao, Y. et al. Allele-specific mechanisms of activation of MEK1 mutants determine their properties. Cancer Discov. 8, 648\u2013661 (2018).","journal-title":"Cancer Discov."},{"key":"68076_CR29","doi-asserted-by":"publisher","first-page":"2339","DOI":"10.1158\/2159-8290.CD-23-0383","volume":"13","author":"NM Sodir","year":"2023","unstructured":"Sodir, N. M. et al. SHP2: a pleiotropic target at the interface of cancer and its microenvironment. Cancer Discov. 13, 2339\u20132355 (2023).","journal-title":"Cancer Discov."},{"key":"68076_CR30","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1517\/14728222.2011.645805","volume":"16","author":"L Santarpia","year":"2012","unstructured":"Santarpia, L., Lippman, S. M. & El-Naggar, A. K. Targeting the MAPK\u2013RAS\u2013RAF signaling pathway in cancer therapy. Expert Opin. Ther. Targets 16, 103\u2013119 (2012).","journal-title":"Expert Opin. Ther. Targets"},{"key":"68076_CR31","doi-asserted-by":"publisher","first-page":"3291","DOI":"10.1038\/sj.onc.1210422","volume":"26","author":"PJ Roberts","year":"2007","unstructured":"Roberts, P. J. & Der, C. J. Targeting the Raf-MEK-ERK mitogen-activated protein kinase cascade for the treatment of cancer. Oncogene 26, 3291\u20133310 (2007).","journal-title":"Oncogene"},{"key":"68076_CR32","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.3390\/cancers11091381","volume":"11","author":"JW Bracht","year":"2019","unstructured":"Bracht, J. W. et al. BRAF mutations classes I, II, and III in NSCLC patients included in the SLLIP trial: the need for a new pre-clinical treatment rationale. Cancers 11, 1381 (2019).","journal-title":"Cancers"},{"key":"68076_CR33","doi-asserted-by":"crossref","unstructured":"Awada, G. et al. Phase II clinical trial of trametinib and low-dose dabrafenib in advanced, previously treated BRAFV600\/NRASQ61 wild-type melanoma (TraMel-WT). JCO Precis. Oncol. 8, e2300493 (2024).","DOI":"10.1200\/PO.23.00493"},{"key":"68076_CR34","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/oncolo\/oyad247","volume":"29","author":"N Rustgi","year":"2024","unstructured":"Rustgi, N. et al. Combined RAF and MEK inhibition to treat activated non-V600 BRAF-altered advanced cancers.  Oncologist 29, 15\u201324 (2024).","journal-title":"Oncologist"},{"key":"68076_CR35","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1038\/s41580-019-0110-x","volume":"20","author":"A Hafner","year":"2019","unstructured":"Hafner, A., Bulyk, M. L., Jambhekar, A. & Lahav, G. The multiple mechanisms that regulate p53 activity and cell fate. Nat. Rev. Mol. Cell Biol. 20, 199\u2013210 (2019).","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"68076_CR36","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-47606-9","volume":"15","author":"S Hobor","year":"2024","unstructured":"Hobor, S. et al. Mixed responses to targeted therapy driven by chromosomal instability through p53 dysfunction and genome doubling. Nat. Commun. 15, 4871 (2024).","journal-title":"Nat. Commun."},{"key":"68076_CR37","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1158\/2326-6066.CIR-20-0401","volume":"9","author":"EJ Lelliott","year":"2021","unstructured":"Lelliott, E. J. et al. Combined BRAF, MEK, and CDK4\/6 inhibition depletes intratumoral immune-potentiating myeloid populations in melanoma. Cancer Immunol. Res. 9, 136\u2013146 (2021).","journal-title":"Cancer Immunol. Res."},{"key":"68076_CR38","doi-asserted-by":"publisher","first-page":"3413","DOI":"10.1158\/0008-5472.CAN-19-3822","volume":"80","author":"I Valencia-Sama","year":"2020","unstructured":"Valencia-Sama, I. et al. NRAS status determines sensitivity to SHP2 inhibitor combination therapies targeting the RAS\u2013MAPK pathway in neuroblastoma. Cancer Res. 80, 3413\u20133423 (2020).","journal-title":"Cancer Res."},{"key":"68076_CR39","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":"68076_CR40","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.1158\/2159-8290.CD-18-0444","volume":"8","author":"C Fedele","year":"2018","unstructured":"Fedele, C. et al. SHP2 inhibition prevents adaptive resistance to MEK inhibitors in multiple cancer models. Cancer Discov. 8, 1237\u20131249 (2018).","journal-title":"Cancer Discov."},{"key":"68076_CR41","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1016\/j.ejca.2008.10.026","volume":"45","author":"EA Eisenhauer","year":"2009","unstructured":"Eisenhauer, E. A. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur. J. Cancer 45, 228\u2013247 (2009).","journal-title":"Eur. J. Cancer"},{"key":"68076_CR42","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","volume":"1","author":"A Liberzon","year":"2015","unstructured":"Liberzon, A. et al. The molecular signatures database (MSigDB) hallmark gene set collection. Cell Syst. 1, 417\u2013425 (2015).","journal-title":"Cell Syst."},{"key":"68076_CR43","doi-asserted-by":"crossref","unstructured":"Elkholi, I. E. et al. Targeting the Dependence on PIK3C3-mTORC1 Signaling in Dormancy-Prone Breast Cancer Cells Blunts Metastasis Initiation. Cancer Res. 85, 2179\u20132198 (2025).","DOI":"10.1158\/0008-5472.CAN-23-2654"},{"key":"68076_CR44","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/j.celrep.2019.03.047","volume":"27","author":"G MacLeod","year":"2019","unstructured":"MacLeod, G. et al. Genome-wide CRISPR-Cas9 screens expose genetic vulnerabilities and mechanisms of temozolomide sensitivity in glioblastoma stem cells. Cell Rep. 27, 971\u2013986.e979 (2019).","journal-title":"Cell Rep."}],"container-title":["Nature Communications"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-68076-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-68076-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-68076-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T13:59:29Z","timestamp":1770213569000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41467-025-68076-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,3]]},"references-count":44,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["68076"],"URL":"https:\/\/doi.org\/10.1038\/s41467-025-68076-7","relation":{},"ISSN":["2041-1723"],"issn-type":[{"value":"2041-1723","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,3]]},"assertion":[{"value":"22 August 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 December 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 January 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Dr. Rose has provided consultation for Advanced Accelerator Applications\/Novartis, EMD Serrono, Merck,\u00a0and Pfizer. Dr. Rose reports research funding from AstraZeneca (Inst), Novartis (Inst), Merck (Inst), Seattle Genetics (Inst), Pfizer (Inst), and Essa Pharma (Inst). Dr. Soria Bretones is an employee of Repare Therapeutics. Dr. King reports research funding from Pfizer (Inst). Dr. Pugh has provided consultation for AstraZeneca, Chrysalis Biomedical Advisors, and Merck (compensated); and receives research support (institutional) from Roche\/Genentech and AstraZeneca. Dr. Shepherd has provided consultation for AstraZeneca and Data and Safety Monitoring Board activity for Merck and Celltrion.\n                      Dr. Leighl reports Research Funding and\/or study materials (Institution)from:\n                      Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Takeda, Guardant Health, Neogenomics;\n                      Honorarium for CME lecture (to institution) from:\n                      Amgen; funding for\n                      travel, accommodations (CME lectures) from:\n                      AstraZeneca, Dava, Guardant Health, Johnson & Johnson, MSD, Roche; and\n                      uncompensated Data Safety Monitoring Board activity for:\n                      Mirati Therapeutics, Daiichi Sankyo. Dr. Razak reported a consulting\/advisory role with Adaptimmune, Bayer, GlaxoSmithKline, Medison, Inhibrx, research funding from Deciphera, Karyopharm Therapeutics, Pfizer, Roche\/Genentech, Bristol Myers Squibb, MedImmune, Amgen, GlaxoSmithKline, Blueprint Medicines, Merck, AbbVie, Adaptimmune, Iterion Therapeutics, Neoleukin Therapeutics, Daiichi Sankyo, Symphogen, Rain Therapeutics, and expert testimony with Medison. Dr. Hansen reported receiving research funds (paid to institution) from: Advancell, AVEO, BMS, Janssen, Macrogenics, MSD, Seagen, Roche, and Tyra Biosciences. Consulting fees (paid personally) from: Astellas, Bayer, Eisai, MSD. Dr. Bedard reported an uncompensated consulting\/advisory role with BMS, Pfizer, Seattle Genetics, Lilly, Amgen, Merck, Gilead Sciences, Repare and research funding from Bristol Myers Squibb (Inst), Sanofi (Inst), AstraZeneca (Inst), Genentech\/Roche (Inst), GlaxoSmithKline (Inst), Novartis (Inst), Nektar (Inst), Merck (Inst), Seattle Genetics (Inst), Immunomedics (Inst), Lilly (Inst), Amgen (Inst), Bicara Therapeutics (Inst), Zymeworks (Inst), Bayer (Inst), Medicenna (Inst), Day One Biopharmaceuticals (Inst). Dr. Siu reported consultant\/advisory roles for: Merck, Pfizer, AstraZeneca, Roche, GlaxoSmithKline, Voronoi, Arvinas, Navire, Relay, Marengo, Daiichi Sankyo, Amgen, Medicenna, LTZ Therapeutics, Tubulis, Marengo, Nerviano, Pangea, Incyte, Gilead; Institutions receives grant\/research support for clinical trials from: Merck, Novartis, Bristol-Myers Squibb, Pfizer\/Seattle Genetics, Boerhinger-Ingelheim, GlaxoSmithKline, Roche\/Genentech, AstraZeneca\/Medimmune, Bayer, Abbvie, Amgen, Symphogen, EMD Serono, 23Me, Daiichi Sankyo, Gilead, Marengo, Incyte, LegoChem, Loxo\/Eli Lilly, Medicenna, Takara; Spouse has leadership position: Treadwell Therapeutics; Spouse has stock ownership: Agios. Dr. Cescon\u00a0reports consultancy and advisory relationships with AstraZeneca, Daiichi Sankyo, Exact Sciences, GenomeRx, Gilead, GlaxoSmithKline, Inivata\/NeoGenomics, Lilly, Merck, Novartis, Pfizer, Roche and SAGA; research funding to their institution from AstraZeneca, GenomeRx, Guardant Health, Grail, Gilead, GlaxoSmithKline, Inivata\/NeoGenomics, Knight, Merck, PearBio, Pfizer, ProteinQure, RayzeBio and Roche.\u00a0Dr. Spreafico reported a consulting\/advisory role with Merck, Bristol-Myers Squibb, and Alents andgrant\/research funding from Novartis, Bristol-Myers Squibb, Symphogen AstraZeneca\/Medimmune, Merck, Bayer, Surface Oncology, Northern Biologics, Janssen Oncology\/Johnson & Johnson, Roche, Regeneron, Alkermes, Array Biopharma\/Pfizer, GSK, NuBiyota, Oncorus, Treadwell, Amgen, ALX Oncology, Nubiyota, Genentech, Seagen, Servier, Incyte, Alentis. All other co-authors report no conflicts of interest.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1323"}}