{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:57:56Z","timestamp":1771894676782,"version":"3.50.1"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:00:00Z","timestamp":1771891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sig Transduct Target Ther"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    DNA profiling is an established method for cancer treatment selection, while RNA profiling remains investigational. We explored associations between DNA and RNA alterations and between the number of genes with altered expression and overall survival (OS) using patient data from IMPACT2 (NCT02152254), a randomized study evaluating molecular profiling for guiding cancer therapy across tumor types. Molecular profiling, including DNA next-generation sequencing, was performed on all 829 patients in the IMPACT2 study. RNA profiling was performed by Tempus for 253 of 829 patients. We evaluated the concordance between DNA and RNA profiling, analyzed OS in 217 treated patients with RNA profiling, and assessed PD-L1 status and number of genes with altered expression. Fifty patients exhibited 58 concordant events, i.e., genomic and expression alteration(s) in the same gene, including 38 copy number events, and 41 patients had statistically significant concordance. We identified 123 gene pairs with significant associations between genomic and expression alterations (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05), including\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations with\n                    <jats:italic>VEGFA<\/jats:italic>\n                    overexpression. The median OS for patients with 0\u20132, 3\u20135, and \u22656 genes with altered expression was 9.8, 11.9, and 6.7 months, respectively (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.03). These results underscore RNA profiling\u2019s potential actionability, and altered expression in \u22656 genes was associated with shorter OS. Significant concordance of\n                    <jats:italic>TP53<\/jats:italic>\n                    alterations with\n                    <jats:italic>VEGFA<\/jats:italic>\n                    overexpression may partially explain tumor response to bevacizumab in\n                    <jats:italic>TP53<\/jats:italic>\n                    -mutant patients.\n                  <\/jats:p>","DOI":"10.1038\/s41392-026-02580-0","type":"journal-article","created":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:01:55Z","timestamp":1771891315000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Concordance analysis of DNA and RNA profiling: The MD Anderson IMPACT2 study in precision oncology"],"prefix":"10.1038","volume":"11","author":[{"given":"Stephanie T.","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet A.","family":"Baysal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Siqing","family":"Fu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David S.","family":"Hong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarina A.","family":"Piha-Paul","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4803-8513","authenticated-orcid":false,"given":"Aung","family":"Naing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jordi","family":"Rodon Ahnert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2154-3309","authenticated-orcid":false,"given":"Timothy A.","family":"Yap","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ecaterina Elena","family":"Dumbrava","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer","family":"Beck","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6816-6072","authenticated-orcid":false,"given":"Funda","family":"Meric-Bernstam","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2713-233X","authenticated-orcid":false,"given":"Apostolia Maria","family":"Tsimberidou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,2,24]]},"reference":[{"key":"2580_CR1","doi-asserted-by":"publisher","first-page":"947","DOI":"10.1056\/NEJMoa0810699","volume":"361","author":"TS Mok","year":"2009","unstructured":"Mok, T. S. et al. Gefitinib or carboplatin-paclitaxel in pulmonary adenocarcinoma. N. Engl. J. Med 361, 947\u2013957 (2009).","journal-title":"N. Engl. J. Med"},{"key":"2580_CR2","doi-asserted-by":"publisher","first-page":"2385","DOI":"10.1056\/NEJMoa1214886","volume":"368","author":"AT Shaw","year":"2013","unstructured":"Shaw, A. T. et al. Crizotinib versus chemotherapy in advanced ALK-positive lung cancer. N. Engl. J. Med 368, 2385\u20132394 (2013).","journal-title":"N. Engl. J. Med"},{"key":"2580_CR3","doi-asserted-by":"publisher","first-page":"809","DOI":"10.1056\/NEJMoa1002011","volume":"363","author":"KT Flaherty","year":"2010","unstructured":"Flaherty, K. T. et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N. Engl. J. Med 363, 809\u2013819 (2010).","journal-title":"N. Engl. J. Med"},{"key":"2580_CR4","doi-asserted-by":"publisher","first-page":"744","DOI":"10.1038\/s41591-019-0407-5","volume":"25","author":"JK Sicklick","year":"2019","unstructured":"Sicklick, J. K. et al. Molecular profiling of cancer patients enables personalized combination therapy: the I-PREDICT study. Nat. Med 25, 744\u2013750 (2019).","journal-title":"Nat. Med"},{"key":"2580_CR5","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1016\/j.immuni.2018.03.023","volume":"48","author":"V Thorsson","year":"2018","unstructured":"Thorsson, V. et al. The Immune Landscape of Cancer. Immunity 48, 812\u2013830.e814 (2018).","journal-title":"Immunity"},{"key":"2580_CR6","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1038\/nrc.2016.66","volume":"16","author":"A Makohon-Moore","year":"2016","unstructured":"Makohon-Moore, A. & Iacobuzio-Donahue, C. A. Pancreatic cancer biology and genetics from an evolutionary perspective. Nat. Rev. Cancer 16, 553\u2013565 (2016).","journal-title":"Nat. Rev. Cancer"},{"key":"2580_CR7","doi-asserted-by":"crossref","unstructured":"Cancer Genome Atlas. Comprehensive molecular portraits of human breast tumours. Nature 490, 61-70 (2012).","DOI":"10.1038\/nature11412"},{"key":"2580_CR8","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms4887","volume":"5","author":"R Akbani","year":"2014","unstructured":"Akbani, R. et al. A pan-cancer proteomic perspective on The Cancer Genome Atlas. Nat. Commun. 5, 3887 (2014).","journal-title":"Nat. Commun."},{"key":"2580_CR9","volume":"6","author":"ST Schmidt","year":"2022","unstructured":"Schmidt, S. T. et al. Shared Nearest Neighbors Approach and Interactive Browser for Network Analysis of a Comprehensive Non-Small-Cell Lung Cancer Data Set. JCO Clin. Cancer Inf. 6, e2200040 (2022).","journal-title":"JCO Clin. Cancer Inf."},{"key":"2580_CR10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/nrg2484","volume":"10","author":"Z Wang","year":"2009","unstructured":"Wang, Z., Gerstein, M. & Snyder, M. RNA-Seq: a revolutionary tool for transcriptomics. Nat. Rev. Genet 10, 57\u201363 (2009).","journal-title":"Nat. Rev. Genet"},{"key":"2580_CR11","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1093\/nar\/gkv007","volume":"43","author":"ME Ritchie","year":"2015","unstructured":"Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 43, e47 (2015).","journal-title":"Nucleic Acids Res"},{"key":"2580_CR12","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1038\/s41571-018-0002-6","volume":"15","author":"MF Berger","year":"2018","unstructured":"Berger, M. F. & Mardis, E. R. The emerging clinical relevance of genomics in cancer medicine. Nat. Rev. Clin. Oncol. 15, 353\u2013365 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2580_CR13","doi-asserted-by":"crossref","unstructured":"Tsimberidou, A. M. et al. Initiative for Molecular Profiling and Advanced Cancer Therapy (IMPACT): An MD Anderson Precision Medicine Study. JCO Precis Oncol 2017 (2017).","DOI":"10.1200\/PO.17.00002"},{"key":"2580_CR14","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1038\/nrclinonc.2018.29","volume":"15","author":"D Fukumura","year":"2018","unstructured":"Fukumura, D., Kloepper, J., Amoozgar, Z., Duda, D. G. & Jain, R. K. Enhancing cancer immunotherapy using antiangiogenics: opportunities and challenges. Nat. Rev. Clin. Oncol. 15, 325\u2013340 (2018).","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"2580_CR15","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1016\/j.cell.2018.02.060","volume":"173","author":"MH Bailey","year":"2018","unstructured":"Bailey, M. H. et al. Comprehensive Characterization of Cancer Driver Genes and Mutations. Cell 173, 371\u2013385.e318 (2018).","journal-title":"Cell"},{"key":"2580_CR16","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1158\/1078-0432.CCR-15-0876","volume":"22","author":"MP Mak","year":"2016","unstructured":"Mak, M. P. et al. A Patient-Derived, Pan-Cancer EMT Signature Identifies Global Molecular Alterations and Immune Target Enrichment Following Epithelial-to-Mesenchymal Transition. Clin. Cancer Res 22, 609\u2013620 (2016).","journal-title":"Clin. Cancer Res"},{"key":"2580_CR17","doi-asserted-by":"publisher","first-page":"3074","DOI":"10.1158\/1078-0432.CCR-18-1942","volume":"25","author":"JJ Luke","year":"2019","unstructured":"Luke, J. J., Bao, R., Sweis, R. F., Spranger, S. & Gajewski, T. F. WNT\/beta-catenin Pathway Activation Correlates with Immune Exclusion across Human Cancers. Clin. Cancer Res 25, 3074\u20133083 (2019).","journal-title":"Clin. Cancer Res"},{"key":"2580_CR18","doi-asserted-by":"crossref","unstructured":"Cristescu, R. et al. Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy. Science 362 (2018).","DOI":"10.1126\/science.aar3593"},{"key":"2580_CR19","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1016\/j.cell.2018.02.052","volume":"173","author":"J Liu","year":"2018","unstructured":"Liu, J. et al. An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics. Cell 173, 400\u2013416.e411 (2018).","journal-title":"Cell"},{"key":"2580_CR20","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1804710","volume":"379","author":"JA Sparano","year":"2018","unstructured":"Sparano, J. A. et al. Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer. N. Engl. J. Med 379, 111\u2013121 (2018).","journal-title":"N. Engl. J. Med"},{"key":"2580_CR21","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1038\/s41591-019-0424-4","volume":"25","author":"J Rodon","year":"2019","unstructured":"Rodon, J. et al. Genomic and transcriptomic profiling expands precision cancer medicine: the WINTHER trial. Nat. Med 25, 751\u2013758 (2019).","journal-title":"Nat. Med"},{"key":"2580_CR22","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41746-025-01471-y","volume":"8","author":"E Fountzilas","year":"2025","unstructured":"Fountzilas, E., Pearce, T., Baysal, M. A., Chakraborty, A. & Tsimberidou, A. M. Convergence of evolving artificial intelligence and machine learning techniques in precision oncology. NPJ Digit Med 8, 75 (2025).","journal-title":"NPJ Digit Med"},{"key":"2580_CR23","doi-asserted-by":"publisher","DOI":"10.1038\/s41698-022-00317-0","volume":"6","author":"HH Vo","year":"2022","unstructured":"Vo, H. H. et al. Challenges and opportunities associated with the MD Anderson IMPACT2 randomized study in precision oncology. NPJ Precis Oncol. 6, 78 (2022).","journal-title":"NPJ Precis Oncol."},{"key":"2580_CR24","unstructured":"Kluyver, T. et al. Jupyter Notebooks-a publishing format for reproducible computational workflows. Positioning and Power in Academic Publishing: Players, Agents and Agendas, 87-90 (2016)."},{"key":"2580_CR25","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/s41586-020-2649-2","volume":"585","author":"Harris","year":"2020","unstructured":"Harris et al. Array programming with NumPy. Nature 585, 357\u2013362 (2020).","journal-title":"Nature"},{"key":"2580_CR26","unstructured":"McKinney, W. in Proceedings of the 9th Python in Science Conference. 51-56 (Austin, TX)."},{"key":"2580_CR27","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1038\/s41592-019-0686-2","volume":"17","author":"P Virtanen","year":"2020","unstructured":"Virtanen, P. et al. SciPy 1.0: fundamental algorithms for scientific computing in Python. Nat. Methods 17, 261\u2013272 (2020).","journal-title":"Nat. Methods"},{"key":"2580_CR28","doi-asserted-by":"publisher","first-page":"1317","DOI":"10.21105\/joss.01317","volume":"4","author":"C Davidson-Pilon","year":"2019","unstructured":"Davidson-Pilon, C. lifelines: survival analysis in Python. J. Open Source Softw. 4, 1317 (2019).","journal-title":"J. Open Source Softw."},{"key":"2580_CR29","doi-asserted-by":"publisher","first-page":"90","DOI":"10.1109\/MCSE.2007.55","volume":"9","author":"JD Hunter","year":"2007","unstructured":"Hunter, J. D. Matplotlib: A 2D graphics environment. Comput Sci. Eng. 9, 90\u201395 (2007).","journal-title":"Comput Sci. Eng."},{"key":"2580_CR30","doi-asserted-by":"publisher","first-page":"3021","DOI":"10.21105\/joss.03021","volume":"6","author":"ML Waskom","year":"2021","unstructured":"Waskom, M. L. Seaborn: statistical data visualization. J. Open Source Softw. 6, 3021 (2021).","journal-title":"J. Open Source Softw."},{"key":"2580_CR31","unstructured":"Hagberg, A., Swart, P. & S Chult, D. in Proceedings of the 7th Python in Science Conference. (eds G\u00e4el Varoquaux, Travis Vaught, & Jarrod Millman) 11-15.(SciPy2008)"},{"key":"2580_CR32","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1002\/sim.3531","volume":"28","author":"S Lydersen","year":"2009","unstructured":"Lydersen, S., Fagerland, M. W. & Laake, P. Recommended tests for association in 2 x 2 tables. Stat. Med 28, 1159\u20131175 (2009).","journal-title":"Stat. Med"},{"key":"2580_CR33","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","volume":"57","author":"B Yoav","year":"1995","unstructured":"Yoav, B. & Yosef, H. Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing. J. R. Stat. Soc. Ser. B (Methodol.) 57, 289\u2013300 (1995).","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"2580_CR34","doi-asserted-by":"publisher","first-page":"1739","DOI":"10.1093\/bioinformatics\/btr260","volume":"27","author":"A Liberzon","year":"2011","unstructured":"Liberzon, A. et al. Molecular signatures database (MSigDB) 3.0. Bioinformatics 27, 1739\u20131740 (2011).","journal-title":"Bioinformatics"},{"key":"2580_CR35","doi-asserted-by":"publisher","first-page":"D380","DOI":"10.1093\/nar\/gkx1013","volume":"46","author":"H Han","year":"2018","unstructured":"Han, H. et al. TRRUST v2: an expanded reference database of human and mouse transcriptional regulatory interactions. Nucleic Acids Res 46, D380\u2013D386 (2018).","journal-title":"Nucleic Acids Res"},{"key":"2580_CR36","doi-asserted-by":"publisher","first-page":"1572","DOI":"10.1136\/bmj.317.7172.1572","volume":"317","author":"JM Bland","year":"1998","unstructured":"Bland, J. M. & Altman, D. G. Survival probabilities (the Kaplan-Meier method). BMJ 317, 1572 (1998).","journal-title":"BMJ"},{"key":"2580_CR37","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1136\/bmj.328.7447.1073","volume":"328","author":"JM Bland","year":"2004","unstructured":"Bland, J. M. & Altman, D. G. The logrank test. BMJ 328, 1073 (2004).","journal-title":"BMJ"},{"key":"2580_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1214\/09-SS051","volume":"4","author":"MP Fay","year":"2010","unstructured":"Fay, M. P. & Proschan, M. A. Wilcoxon-Mann-Whitney or t-test? On assumptions for hypothesis tests and multiple interpretations of decision rules. Stat. Surv. 4, 1\u201339 (2010).","journal-title":"Stat. Surv."}],"container-title":["Signal Transduction and Targeted Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02580-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02580-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02580-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T00:01:57Z","timestamp":1771891317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41392-026-02580-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,24]]},"references-count":38,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["2580"],"URL":"https:\/\/doi.org\/10.1038\/s41392-026-02580-0","relation":{},"ISSN":["2059-3635"],"issn-type":[{"value":"2059-3635","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,24]]},"assertion":[{"value":"12 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 December 2025","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 January 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2026","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"S.F. reports research support from Abbisko, Antengene, BeiGene, BeyongSpring Pharmaceuticals, BioAtla, Boehringer Ingelheim, CUE Biopharma, DEKA Biosciences, Eli Lilly & Co., Exelixis, Greenfire Bio, Hookipa Biotech, IMV, Innovent Biologics, Jazz Pharmaceuticals, K-Group Beta, Lantern Pharma, Lyvgen Biopharm, MacroGenics, MediLink Therapeutics, Millennium Pharmaceuticals, Nerviano Medical Sciences, NeuPharma, NextCure, Ningbo NewBay Technology Development, Novartis, NovoCure, Nykode Therapeutics AS, Parexel International, PharmaMar USA, Pionyr Immunotherapeutics, PureTech Health, Qurgen, Shanghai Huaota Biopharmaceutical, Sellas Life Sciences Group, Soricimed Biopharma, SQZ Biotechnologies, Sumitomo Dainippon, Taiho Oncology, NCCN, Treadwell Therapeutics, Turnstone Biologics, Tyligand Bioscience, and Virogin Biotech. D.S.H. reports research support from AbbVie, Adaptimmune, Adlai-Nortye, Amgen, Astelles, Astra-Zeneca, Bayer, Biomea, Bristol-Myers Squibb, Daiichi-Sankyo, Deciphera, Eisai, Eli Lilly, Endeavor, Erasca, F. Hoffmann-LaRoche, Fate Therapeutics, Genentech, Genmab, Immunogenesis, Infinity, Kyowa Kirin, Merck, Mirati, Navier, NCI-CTEP, Novartis, Numab, Pfizer, Pyramid Bio, Revolution Medicine, SeaGen, STCube, Takeda, TCR2, Turning Point Therapeutics, VM Oncology; consulting\/speaker\/advisory roles for 28Bio, Abbvie, Acuta, Adaptimmune, Alkermes, Alpha Insights, Amgen, Affini-T, Astellas, Aumbiosciences, Axiom, Baxter, Bayer, Boxer Capital, BridgeBio, CARSgen, CLCC, COG, COR2ed, Cowen, Ecor1, EDDC, Erasca, Exelixis, Fate Therapeutics, F. Hoffmann-La Roche, Genentech, Gennao Bio, Gilead, GLG, Group H, Guidepoint, HCW Precision Oncology, Immunogenesis, Incyte, Inhibrix, InduPro, Janssen, Jounce Therapeutics Inc, Lan-Bio, Liberium, MedaCorp, Medscape, Novartis, Numab, Oncologia Brasil, ORI Capital, Pfizer, Pharma Intelligence, POET Congress, Prime Oncology, Projects in Knowledge, Quanta, RAIN, Ridgeline, Revolution Medicine SeaGen, Stanford, STCube, Takeda, Tavistock, Trieza Therapeutics, T-Knife, Turning Point Therapeutics, WebMD, YingLing Pharma, and Ziopharm; travel support from AACR, ASCO, CLCC, Bayer, Genmab, SITC, and Telperian; and other ownership interests for Molecular Match (advisor), OncoResponse (founder, advisor), and Telperian (founder, advisor). S.A.P.P. reports research funding (to institution) from AbbVie, ABM Therapeutics, Acepodia, Alkermes, Aminex Therapeutics, BioMarin Pharmaceutical, Boehringer Ingelheim, Bristol Myers Squib, Cerulean Pharma, Chugai Pharmaceutical Co., Curis, Cyclacel Pharmaceuticals, Daiichi Sankyo, Dohme, Eli Lilly, ENB Therapeutics, Epigenetix, Five Prime Therapeutics, F-Star Beta Limited, F-Star Therapeutics, Gene Quantum, Genmab A\/S, Gilead Sciences, GlaxoSmithKline, Helix BioPharma, Hengrui Pharmaceuticals, HiberCell, Immunomedics, Incyte, Jacobio Pharmaceuticals, Jazz Pharmaceuticals, Jiangsu Simcere Pharmaceutical Co., Loxo Oncology, Lytix Biopharma AS, Medimmune, Medivation, Merck Sharp, Nectin Therapeutics, Novartis Pharmaceuticals, Nurix, OncoNano Medicine, Pieris Pharmaceuticals, Pfizer, Phanes Therapeutics, Principia Biopharma, ProFoundBio US, Puma Biotechnology, Purinomia Biotech, Rapt Therapeutics, Replimune; Roche\/Blueprint, Seattle Genetics, Silverback Therapeutics, Shasqi, Synlogic Therapeutics, Taiho Oncology, Tallac Therapeutics, Tesaro, Theradex Oncology, Toragen Therapeutics, TransThera Bio, Xencor, ZielBio; and consulting for CRC Oncology and Lilly USA. A.N. reports research funding from NCI, EMD Serono, MedImmune, Healios Onc. Nutrition, Atterocor\/Millendo, Amplimmune, ARMO BioSciences, Karyopharm Therapeutics, Incyte, Novartis, Regeneron, Merck, Bristol-Myers Squibb, Pfizer, CytomX Therapeutics, Neon Therapeutics, Calithera Biosciences, TopAlliance Biosciences, Eli Lilly, Kymab, PsiOxus, Arcus Biosciences, NeoImmuneTech, Immune-Onc Therapeutics, Surface Oncology, Monopteros Therapeutics, BioNTech SE, Seven & Eight Biopharma, and SOTIO Biotech AG; consulting\/advisory board role for CTI, Deka Biosciences, Janssen Biotech, NGM Bio, PsiOxus Therapeutics, Immune-Onc Therapeutics, STCube Pharmaceuticals, OncoSec KEYNOTE-695, Genome & Company, CytomX Therapeutics, Nouscom, Merck Sharp & Dohme Corp, Servier, Lynx Health, AbbVie, and PsiOxus; travel support from ARMO BioSciences, NeoImmuneTech, and NGM Biopharmaceuticals; honoraria from AKH Inc, The Lynx Group, Society for Immunotherapy of Cancer (SITC), Korean Society of Medical Oncology (KSMO), Scripps Cancer Care Symposium, ASCO Direct Oncology Highlights, European Society for Medical Oncology (ESMO), and CME Outfitters. T.A.Y. reports research support from Artios, AstraZeneca, Bayer, Beigene, BioNTech, Blueprint, BMS, Boundless Bio, Clovis, Constellation, CPRIT, Cyteir, Department of Defense, Eli Lilly, EMD Serono, Exelixis, Forbius, F-Star, GlaxoSmithKline, Genentech, Gilead, Golfers against Cancer, Haihe, Ideaya, ImmuneSensor, Insilico Medicine, Ionis, Ipsen, Jounce, Karyopharm, KSQ, Kyowa, Merck, Mirati, Novartis, NIH\/NCI, Pfizer, Pliant, Prelude, Ribon Therapeutics, Regeneron, Repare, Roche, Rubius, Sanofi, Scholar Rock, Seattle Genetics, Synnovation, Tango, Tesaro, V Foundation, Vivace, Zenith, and Zentalis; consulting for AbbVie, Acrivon, Adagene, Almac, Aduro, Amgen, Amphista, Artios, Astex, AstraZeneca, Athena, Atrin, Avenzo, Avoro, Axiom, Baptist Health Systems, Bayer, Beigene, BioCity Pharma, Blueprint, Boxer, BridGene Biosciences, Bristol Myers Squibb, C4 Therapeutics, Calithera, Cancer Research UK, Carrick Therapeutics, Circle Pharma, Clovis, Cybrexa, Daiichi Sankyo, Dark Blue Therapeutics, Debiopharm, Diffusion, Duke Street Bio, 858 Therapeutics, EcoR1 Capital, Ellipses Pharma, EMD Serono, Entos, FoRx Therapeutics AG, F-Star, Genesis Therapeutics, Genmab, Glenmark, GLG, Globe Life Sciences, Grey Wolf Therapeutics, GSK, Guidepoint, Ideaya Biosciences, Idience, Ignyta, I-Mab, ImmuneSensor, Impact Therapeutics, Institut Gustave Roussy, Intellisphere, Jansen, Joint Scientific Committee for Phase I Trials in Hong Kong, Kyn, Kyowa Kirin, MEI pharma, Mereo, Merck, Merit, Monte Rosa Therapeutics, Natera, Nested Therapeutics, Nexys, Nimbus, Novocure, Odyssey Therapeutics, OHSU, OncoSec, Ono Pharma, Onxeo, PanAngium Therapeutics, Pegascy, PER, Pfizer, Piper-Sandler, Pliant Therapeutics, Prelude Therapeutics, Prolynx, Protai Bio, Radiopharma Theranostics, Repare, resTORbio, Roche, Ryvu Therapeutics, SAKK, Sanofi, Schrodinger, Servier, Synnovation, Synthis Therapeutics, Tango, TCG Crossover, TD2, Terremoto Biosciences, Tessellate Bio, Theragnostics, Terns Pharmaceuticals, Thryv Therapeutics, Tolremo, Tome, Trevarx Biomedical, Varian, Veeva, Versant, Vibliome, Voronoi, Xinthera, Zai Labs, and ZielBio; and stock ownership in Seagen. E.E.D. reports research or grant funding from Bayer Healthcare Pharmaceuticals, Immunocore, Amgen, Aileron Therapeutics, Compugen, TRACON Pharmaceuticals, UnumTherapeutics, Immunomedics, Bolt Therapeutics, Aprea Therapeutics, Bellicum Pharmaceuticals, PMV Pharma, Triumvira Immunologics, Seagen, Mereo BioPharma 5, Sanofi, Rain Oncology, Astex Pharmaceuticals, SOTIO, Poseida Therapeutics, Mersana Therapeutics, Genentech, Boehringer Ingelheim, Dragonfly Therapeutics, A2A Pharmaceuticals, Volastra Therapeutics, and AstraZeneca. E.E.D. has consulted for or was on an advisory board of Bolt Therapeutics, Mersana Therapeutics, Orum Therapeutics, Summit Therapeutics, Fate Therapeutics, and PMV Pharma. E.D. has been a speaker for PMV Pharma and has received travel, accommodations, and\/or expenses from the American Society of Clinical Oncology (ASCO), the Li-Fraumeni Syndrome Association (LFSA), the Korean Society of Medical Oncology (KSMO), Rain Oncology, the Banner MD Anderson Cancer Center, and Triumvira Immunologics. J.R. reports research funding from 3H Pharmaceuticals; AADI Bioscience, Amgen, AstraZenneca, Beigene, Bicycle Therapeutics, BioAlta, Biotheryx, Blueprint Medicines, Bridgebio Pharma, C4 Therapeutics, Cancer Core Europe, Debio, Fog Pharmaceuticals, ForeBio, FusionPharma, GlaxoSmithKline, Hummingbird, Hutchinson MediPharma, Ideaya, Incyte, Kelun-Biotech, Kinnate, Linnaeus Therapeutics, Loxo Oncology, MapKure, Merck Sharp & Dohme, Merus, Mirati, MonteRosa, Novartis, Nuvectis Pharma, Pfizer, Relay, Roche Pharmaceuticals, Scorpion Therapeutics, Storm Therapeutics, Symphogen, Taiho, Tango Therapeutics, Tyra, Vall d\u2019Hebron Institute of and Oncology\/Cancer Core Europe, Yingli; consulting\/advisory board role for AADI Bioscience, Amgen, Boxer Capital, Bridgebio, Chinese University of Hong Kong, Cogent Biosciences, EcoR1 Capital, Ellipses Pharma, Guidepoint; IONCTURA, Mekanistic, Merus, Molecular Partners, MonteRosa, Sardona, Tang Advisors, Vall d\u2019Hebron Institute of Oncology\/Ministero De Empleo Y Seguridad Social; travel support from European Society for Medical Oncology and Loxo Oncology; and other support from Boxer Capital, Chinese University of Hong Kong, Guidepoint; Tang Advisors, and Vall d\u2019Hebron Institute of Oncology\/Ministero De Empleo Y Seguridad Social. F.M.B. reports consulting for AbbVie, Aduro BioTech Inc., Alkermes, AstraZeneca, Daiichi Sankyo Co. Ltd., Calibr (a division of Scripps Research), DebioPharm, Ecor1 Capital, eFFECTOR Therapeutics, F. Hoffman-La Roche Ltd., GT Apeiron, Genentech Inc., Harbinger Health, IBM Watson, Incyte, Infinity Pharmaceuticals, Jackson Laboratory, Kolon Life Science, LegoChem Bio, Lengo Therapeutics, Menarini Group, OrigiMed, PACT Pharma, Parexel International, Pfizer Inc., Protai Bio Ltd., Samsung Bioepis, Seattle Genetics Inc., Tallac Therapeutics, Tyra Biosciences, Xencor, Zymeworks; advisory Committee membership for Black Diamond, Biovica, Eisai, FogPharma, Immunomedics, Inflection Biosciences, Karyopharm Therapeutics, Loxo Oncology, Mersana Therapeutics, OnCusp Therapeutics, Puma Biotechnology Inc., Seattle Genetics, Sanofi, Silverback Therapeutics, Spectrum Pharmaceuticals, Theratechnologies, Zentalis; Sponsored Research (to the institution) from Aileron Therapeutics Inc. AstraZeneca, Bayer Healthcare Pharmaceutical, Calithera Biosciences Inc., Curis Inc., CytomX Therapeutics Inc., Daiichi Sankyo Co. Ltd., Debiopharm International, eFFECTOR Therapeutics, Genentech Inc., Guardant Health Inc., Klus Pharma, Takeda Pharmaceutical, Novartis, Puma Biotechnology Inc., Taiho Pharmaceutical Co.; Honoraria from Dava Oncology; and Other (Travel Related) from European Organization for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), Cholangiocarcinoma Foundation, Dava Oncology. A.M.T. reports grants from OBI Pharma, Agenus, Vividion, MacroGenics, AbbVie, Immatics, Novocure, Tachyon, Parker Institute for Cancer Immunotherapy, Tempus, and Tvardi Therapeutics and personal fees from Avstera Therapeutics, BioEclipse, BrYet, Diaccurate, MacroGenics, NEX-I, and Vincerx during the course of the study. S.T.S., M.B. 0042aysal, and J.B. do not have conflicts of interest to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"68"}}