{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T23:56:15Z","timestamp":1792454175059,"version":"4.5.0"},"reference-count":56,"publisher":"American Association for Cancer Research (AACR)","issue":"11","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":98,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100013874","name":"Hope Funds for Cancer Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100013874","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"crossref","award":["740469"],"award-info":[{"award-number":["740469"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100005984","name":"Dr. Miriam and Sheldon G. Adelson Medical Research Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100005984","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,11,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>Anticancer therapies have been limited by the emergence of mutations and other adaptations. In bacteria, antibiotics activate the SOS response, which mobilizes error-prone factors that allow for continuous replication at the cost of mutagenesis. We investigated whether the treatment of lung cancer with EGFR inhibitors (EGFRi) similarly engages hypermutators. In cycling drug-tolerant persister (DTP) cells and in EGFRi-treated patients presenting residual disease, we observed upregulation of GAS6, whereas ablation of GAS6's receptor, AXL, eradicated resistance. Reciprocally, AXL overexpression enhanced DTP survival and accelerated the emergence of T790M, an EGFR mutation typical to resistant cells. Mechanistically, AXL induces low-fidelity DNA polymerases and activates their organizer, RAD18, by promoting neddylation. Metabolomics uncovered another hypermutator, AXL-driven activation of MYC, and increased purine synthesis that is unbalanced by pyrimidines. Aligning anti-AXL combination treatments with the transition from DTPs to resistant cells cured patient-derived xenografts. Hence, similar to bacteria, tumors tolerate therapy by engaging pharmacologically targetable endogenous mutators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>EGFR-mutant lung cancers treated with kinase inhibitors often evolve resistance due to secondary mutations. We report that in similarity to the bacterial SOS response stimulated by antibiotics, endogenous mutators are activated in drug-treated cells, and this heralds tolerance. Blocking the process prevented resistance in xenograft models, which offers new treatment strategies.<\/jats:p>\n                    <jats:p>This article is highlighted in the In This Issue feature, p. 2483<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-22-0111","type":"journal-article","created":{"date-parts":[[2022,7,27]],"date-time":"2022-07-27T14:45:45Z","timestamp":1658933145000},"page":"2666-2683","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":111,"title":["AXL and Error-Prone DNA Replication Confer Drug Resistance and Offer Strategies to Treat EGFR-Mutant Lung Cancer"],"prefix":"10.1158","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3415-6113","authenticated-orcid":false,"given":"Ashish","family":"Noronha","sequence":"first","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2970-6739","authenticated-orcid":false,"given":"Nishanth","family":"Belugali Nataraj","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8564-0848","authenticated-orcid":false,"given":"Joo Sang","family":"Lee","sequence":"additional","affiliation":[{"name":"2Cancer Data Science Lab, NCI, NIH, Bethesda, Maryland."},{"name":"3Next-Gen Medicine Lab, School of Medicine and Department of Artificial Intelligence, Sungkyunkwan University, Suwon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8027-927X","authenticated-orcid":false,"given":"Benny","family":"Zhitomirsky","sequence":"additional","affiliation":[{"name":"4Broad Institute of MIT and Harvard, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2509-4504","authenticated-orcid":false,"given":"Yaara","family":"Oren","sequence":"additional","affiliation":[{"name":"5Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, Massachusetts."},{"name":"6Department of Cell Biology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4121-7754","authenticated-orcid":false,"given":"Sara","family":"Oster","sequence":"additional","affiliation":[{"name":"7Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4485-1355","authenticated-orcid":false,"given":"Moshit","family":"Lindzen","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8704-481X","authenticated-orcid":false,"given":"Saptaparna","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"8Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6049-2690","authenticated-orcid":false,"given":"Rainer","family":"Will","sequence":"additional","affiliation":[{"name":"9Genomics and Proteomics Core Facility, German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soma","family":"Ghosh","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1353-260X","authenticated-orcid":false,"given":"Arturo","family":"Simoni-Nieves","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-9457","authenticated-orcid":false,"given":"Aakanksha","family":"Verma","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8484-3897","authenticated-orcid":false,"given":"Rishita","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3833-0032","authenticated-orcid":false,"given":"Simone","family":"Borgoni","sequence":"additional","affiliation":[{"name":"10Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9018-6811","authenticated-orcid":false,"given":"Welles","family":"Robinson","sequence":"additional","affiliation":[{"name":"2Cancer Data Science Lab, NCI, NIH, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2688-0603","authenticated-orcid":false,"given":"Sanju","family":"Sinha","sequence":"additional","affiliation":[{"name":"2Cancer Data Science Lab, NCI, NIH, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9604-2229","authenticated-orcid":false,"given":"Alexander","family":"Brandis","sequence":"additional","affiliation":[{"name":"11Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0557-8341","authenticated-orcid":false,"given":"D. Lucas","family":"Kerr","sequence":"additional","affiliation":[{"name":"12Department of Medicine, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6556-067X","authenticated-orcid":false,"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"12Department of Medicine, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4659-5260","authenticated-orcid":false,"given":"Arunachalam","family":"Sekar","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7595-1359","authenticated-orcid":false,"given":"Suvendu","family":"Giri","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0597-1004","authenticated-orcid":false,"given":"Youngmin","family":"Chung","sequence":"additional","affiliation":[{"name":"3Next-Gen Medicine Lab, School of Medicine and Department of Artificial Intelligence, Sungkyunkwan University, Suwon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6397-3123","authenticated-orcid":false,"given":"Diana","family":"Drago-Garcia","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6839-6337","authenticated-orcid":false,"given":"Brian P.","family":"Danysh","sequence":"additional","affiliation":[{"name":"4Broad Institute of MIT and Harvard, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7966-0065","authenticated-orcid":false,"given":"Mattia","family":"Lauriola","sequence":"additional","affiliation":[{"name":"13Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1749-150X","authenticated-orcid":false,"given":"Michelangelo","family":"Fiorentino","sequence":"additional","affiliation":[{"name":"13Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2678-0714","authenticated-orcid":false,"given":"Andrea","family":"Ardizzoni","sequence":"additional","affiliation":[{"name":"13Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy."},{"name":"14Medical Oncology IRCCS Azienda Ospedaliero, University of Bologna, Bologna, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4311-7172","authenticated-orcid":false,"given":"Moshe","family":"Oren","sequence":"additional","affiliation":[{"name":"8Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8134-3651","authenticated-orcid":false,"given":"Collin M.","family":"Blakely","sequence":"additional","affiliation":[{"name":"12Department of Medicine, University of California, San Francisco, California."},{"name":"15Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3767-8902","authenticated-orcid":false,"given":"Jideofor","family":"Ezike","sequence":"additional","affiliation":[{"name":"4Broad Institute of MIT and Harvard, Cambridge, Massachusetts."},{"name":"16Computational and Systems Biology Program, Massachusetts Institute of Technology, Cambridge, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4683-3174","authenticated-orcid":false,"given":"Stefan","family":"Wiemann","sequence":"additional","affiliation":[{"name":"10Division of Molecular Genome Analysis, German Cancer Research Center (DKFZ), Heidelberg, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7872-5074","authenticated-orcid":false,"given":"Laxmi","family":"Parida","sequence":"additional","affiliation":[{"name":"17Thomas J. Watson Research Center, IBM Research, Yorktown Heights, New York."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5734-4128","authenticated-orcid":false,"given":"Trever G.","family":"Bivona","sequence":"additional","affiliation":[{"name":"12Department of Medicine, University of California, San Francisco, California."},{"name":"15Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California."},{"name":"18Department of Cellular and Molecular Pharmacology, University of California, San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6034-023X","authenticated-orcid":false,"given":"Rami I.","family":"Aqeilan","sequence":"additional","affiliation":[{"name":"7Lautenberg Center for Immunology and Cancer Research, Institute for Medical Research Israel-Canada, Hebrew University-Hadassah Medical School, Jerusalem, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2547-4814","authenticated-orcid":false,"given":"Joan S.","family":"Brugge","sequence":"additional","affiliation":[{"name":"6Department of Cell Biology, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3293-3158","authenticated-orcid":false,"given":"Aviv","family":"Regev","sequence":"additional","affiliation":[{"name":"19Genentech Inc., South San Francisco, California."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0936-0753","authenticated-orcid":false,"given":"Gad","family":"Getz","sequence":"additional","affiliation":[{"name":"4Broad Institute of MIT and Harvard, Cambridge, Massachusetts."},{"name":"20Cancer Center and Department of Pathology, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston, Massachusetts."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7862-3940","authenticated-orcid":false,"given":"Eytan","family":"Ruppin","sequence":"additional","affiliation":[{"name":"2Cancer Data Science Lab, NCI, NIH, Bethesda, Maryland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4168-7884","authenticated-orcid":false,"given":"Yosef","family":"Yarden","sequence":"additional","affiliation":[{"name":"1Department of Biological Regulation, Weizmann Institute of Science, Rehovot, Israel."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2022,7,27]]},"reference":[{"key":"2025121006534094500_bib1","first-page":"355","article-title":"SOS repair hypothesis: phenomenology of an inducible DNA repair which is accompanied by mutagenesis","volume":"5A","author":"Radman","year":"1975","journal-title":"Basic Life Sci"},{"key":"2025121006534094500_bib2","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1126\/science.1226683","article-title":"Identity and function of a large gene network underlying mutagenic repair of DNA breaks","volume":"338","author":"Al Mamun","year":"2012","journal-title":"Science"},{"key":"2025121006534094500_bib3","doi-asserted-by":"crossref","first-page":"1126","DOI":"10.1111\/1574-6976.12077","article-title":"SOS, the formidable strategy of bacteria against aggressions","volume":"38","author":"Baharoglu","year":"2014","journal-title":"FEMS Microbiol Rev"},{"key":"2025121006534094500_bib4","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1146\/annurev-cancerbio-050216-121919","article-title":"Stress-induced mutagenesis: implications in cancer and drug resistance","volume":"1","author":"Fitzgerald","year":"2017","journal-title":"Annu Rev Cancer Biol"},{"key":"2025121006534094500_bib5","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1126\/science.aav4474","article-title":"Adaptive mutability of colorectal cancers in response to targeted therapies","volume":"366","author":"Russo","year":"2019","journal-title":"Science"},{"key":"2025121006534094500_bib6","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1126\/science.aau8768","article-title":"MTOR signaling orchestrates stress-induced mutagenesis, facilitating adaptive evolution in cancer","volume":"368","author":"Cipponi","year":"2020","journal-title":"Science"},{"key":"2025121006534094500_bib7","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1158\/2159-8290.CD-12-0012","article-title":"Circumventing cancer drug resistance in the era of personalized medicine","volume":"2","author":"Garraway","year":"2012","journal-title":"Cancer Discov"},{"key":"2025121006534094500_bib8","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.ccell.2018.03.025","article-title":"A convergence-based framework for cancer drug resistance","volume":"33","author":"Konieczkowski","year":"2018","journal-title":"Cancer Cell"},{"key":"2025121006534094500_bib9","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cell.2010.02.027","article-title":"A chromatin-mediated reversible drug-tolerant state in cancer cell subpopulations","volume":"141","author":"Sharma","year":"2010","journal-title":"Cell"},{"key":"2025121006534094500_bib10","doi-asserted-by":"crossref","first-page":"e73","DOI":"10.1371\/journal.pmed.0020073","article-title":"Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain","volume":"2","author":"Pao","year":"2005","journal-title":"PLoS Med"},{"key":"2025121006534094500_bib11","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1056\/NEJMoa044238","article-title":"EGFR mutation and resistance of non-small-cell lung cancer to gefitinib","volume":"352","author":"Kobayashi","year":"2005","journal-title":"N Engl J Med"},{"key":"2025121006534094500_bib12","doi-asserted-by":"crossref","first-page":"5530","DOI":"10.1158\/1078-0432.CCR-10-2571","article-title":"New strategies in overcoming acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in lung cancer","volume":"17","author":"Oxnard","year":"2011","journal-title":"Clin Cancer Res"},{"key":"2025121006534094500_bib13","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1126\/science.1141478","article-title":"MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling","volume":"316","author":"Engelman","year":"2007","journal-title":"Science"},{"key":"2025121006534094500_bib14","doi-asserted-by":"crossref","first-page":"294","DOI":"10.15252\/emmm.201708076","article-title":"An oligoclonal antibody durably overcomes resistance of lung cancer to third-generation EGFR inhibitors","volume":"10","author":"Mancini","year":"2018","journal-title":"EMBO Mol Med"},{"key":"2025121006534094500_bib15","doi-asserted-by":"crossref","first-page":"5610","DOI":"10.1158\/1078-0432.CCR-18-0450","article-title":"A combination of approved antibodies overcomes resistance of lung cancer to osimertinib by blocking bypass pathways","volume":"24","author":"Romaniello","year":"2018","journal-title":"Clin Cancer Res"},{"key":"2025121006534094500_bib16","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1038\/s41467-018-08074-0","article-title":"AXL confers intrinsic resistance to osimertinib and advances the emergence of tolerant cells","volume":"10","author":"Taniguchi","year":"2019","journal-title":"Nat Commun"},{"key":"2025121006534094500_bib17","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1038\/ng.2330","article-title":"Activation of the AXL kinase causes resistance to EGFR-targeted therapy in lung cancer","volume":"44","author":"Zhang","year":"2012","journal-title":"Nat Genet"},{"key":"2025121006534094500_bib18","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1158\/1078-0432.CCR-07-2248","article-title":"Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer","volume":"14","author":"Engelman","year":"2008","journal-title":"Clin Cancer Res"},{"key":"2025121006534094500_bib19","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1158\/0008-5472.CAN-20-3555","article-title":"Host-dependent phenotypic resistance to EGFR tyrosine kinase inhibitors","volume":"81","author":"Haga","year":"2021","journal-title":"Cancer Res"},{"key":"2025121006534094500_bib20","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrc3847","article-title":"The TAM family: phosphatidylserine sensing receptor tyrosine kinases gone awry in cancer","volume":"14","author":"Graham","year":"2014","journal-title":"Nat Rev Cancer"},{"key":"2025121006534094500_bib21","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1016\/j.trecan.2018.01.001","article-title":"The genetic\/non-genetic duality of drug \u2018resistance\u2019 in cancer","volume":"4","author":"Salgia","year":"2018","journal-title":"Trends Cancer"},{"key":"2025121006534094500_bib22","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/sj.bjc.6603949","article-title":"Evaluation of epidermal growth factor receptor mutation status in serum DNA as a predictor of response to gefitinib (IRESSA)","volume":"97","author":"Kimura","year":"2007","journal-title":"Br J Cancer"},{"key":"2025121006534094500_bib23","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1038\/s41586-021-03796-6","article-title":"Cycling cancer persister cells arise from lineages with distinct programs","volume":"596","author":"Oren","year":"2021","journal-title":"Nature"},{"key":"2025121006534094500_bib24","first-page":"1100007","article-title":"Clonal evolution and heterogeneity of osimertinib acquired resistance mechanisms in EGFR mutant lung cancer","volume":"1","author":"Roper","year":"2020","journal-title":"Cell Rep Med"},{"key":"2025121006534094500_bib25","doi-asserted-by":"crossref","first-page":"15058","DOI":"10.1038\/ncomms15058","article-title":"BLISS is a versatile and quantitative method for genome-wide profiling of DNA double-strand breaks","volume":"8","author":"Yan","year":"2017","journal-title":"Nat Commun"},{"key":"2025121006534094500_bib26","doi-asserted-by":"crossref","first-page":"2633","DOI":"10.1101\/gad.13.20.2633","article-title":"XRCC3 promotes homology-directed repair of DNA damage in mammalian cells","volume":"13","author":"Pierce","year":"1999","journal-title":"Genes Dev"},{"key":"2025121006534094500_bib27","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1146\/annurev-biochem-062917-012405","article-title":"Translesion and repair DNA polymerases: diverse structure and mechanism","volume":"87","author":"Yang","year":"2018","journal-title":"Annu Rev Biochem"},{"key":"2025121006534094500_bib28","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1080\/15384101.2018.1456296","article-title":"Diverse roles of RAD18 and Y-family DNA polymerases in tumorigenesis","volume":"17","author":"Yang","year":"2018","journal-title":"Cell Cycle"},{"key":"2025121006534094500_bib29","doi-asserted-by":"crossref","first-page":"1232","DOI":"10.1016\/j.cell.2020.07.017","article-title":"Therapy-induced evolution of human lung cancer revealed by single-cell RNA sequencing","volume":"182","author":"Maynard","year":"2020","journal-title":"Cell"},{"key":"2025121006534094500_bib30","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/nature01965","article-title":"Control of spontaneous and damage-induced mutagenesis by SUMO and ubiquitin conjugation","volume":"425","author":"Stelter","year":"2003","journal-title":"Nature"},{"key":"2025121006534094500_bib31","doi-asserted-by":"crossref","first-page":"1821","DOI":"10.1126\/science.1120615","article-title":"Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis","volume":"310","author":"Bienko","year":"2005","journal-title":"Science"},{"key":"2025121006534094500_bib32","doi-asserted-by":"crossref","first-page":"12105","DOI":"10.1038\/ncomms12105","article-title":"A neomorphic cancer cell-specific role of MAGE-A4 in trans-lesion synthesis","volume":"7","author":"Gao","year":"2016","journal-title":"Nat Commun"},{"key":"2025121006534094500_bib33","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1016\/j.bbrc.2018.12.072","article-title":"NEDDylation regulates RAD18 ubiquitination and localization in response to oxidative DNA damage","volume":"508","author":"Guan","year":"2018","journal-title":"Bichem Biophys Res Commun"},{"key":"2025121006534094500_bib34","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1038\/nm.4040","article-title":"Tumor cells can follow distinct evolutionary paths to become resistant to epidermal growth factor receptor inhibition","volume":"22","author":"Hata","year":"2016","journal-title":"Nat Med"},{"key":"2025121006534094500_bib35","doi-asserted-by":"crossref","first-page":"E4442","DOI":"10.1073\/pnas.1618714114","article-title":"Alterations in cellular metabolism triggered by URA7 or GLN3 inactivation cause imbalanced dNTP pools and increased mutagenesis","volume":"114","author":"Schmidt","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025121006534094500_bib36","doi-asserted-by":"crossref","first-page":"6105","DOI":"10.1128\/MCB.17.10.6105","article-title":"Identification of RNR4, encoding a second essential small subunit of ribonucleotide reductase in Saccharomyces cerevisiae","volume":"17","author":"Huang","year":"1997","journal-title":"Mol Cell Biol"},{"key":"2025121006534094500_bib37","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.cell.2011.03.044","article-title":"Nucleotide deficiency promotes genomic instability in early stages of cancer development","volume":"145","author":"Bester","year":"2011","journal-title":"Cell"},{"key":"2025121006534094500_bib38","doi-asserted-by":"crossref","first-page":"1559","DOI":"10.1016\/j.cell.2018.07.019","article-title":"Urea cycle dysregulation generates clinically relevant genomic and biochemical signatures","volume":"174","author":"Lee","year":"2018","journal-title":"Cell"},{"key":"2025121006534094500_bib39","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1126\/science.aad0489","article-title":"mTORC1 induces purine synthesis through control of the mitochondrial tetrahydrofolate cycle","volume":"351","author":"Ben-Sahra","year":"2016","journal-title":"Science"},{"key":"2025121006534094500_bib40","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/1878-0261.12395","article-title":"Transcriptional upregulation of c-MYC by AXL confers epirubicin resistance in esophageal adenocarcinoma","volume":"12","author":"Hong","year":"2018","journal-title":"Mol Oncol"},{"key":"2025121006534094500_bib41","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1038\/s43018-020-0106-7","article-title":"Targeting purine synthesis in ASS1-expressing tumors enhances the response to immune checkpoint inhibitors","volume":"1","author":"Keshet","year":"2020","journal-title":"Nature Cancer"},{"key":"2025121006534094500_bib42","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1016\/j.cell.2017.11.013","article-title":"Myc cooperates with ras by programming inflammation and immune suppression","volume":"171","author":"Kortlever","year":"2017","journal-title":"Cell"},{"key":"2025121006534094500_bib43","doi-asserted-by":"crossref","first-page":"e6693","DOI":"10.1371\/journal.pone.0006693","article-title":"A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response","volume":"4","author":"Chandriani","year":"2009","journal-title":"PLoS One"},{"key":"2025121006534094500_bib44","doi-asserted-by":"crossref","first-page":"S467","DOI":"10.1245\/s10434-012-2795-3","article-title":"Higher expression of receptor tyrosine kinase Axl, and differential expression of its ligand, Gas6, predict poor survival in lung adenocarcinoma patients","volume":"20","author":"Ishikawa","year":"2013","journal-title":"Ann Surg Oncol"},{"key":"2025121006534094500_bib45","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1158\/1078-0432.CCR-15-0620","article-title":"Afatinib plus cetuximab delays resistance compared to single-agent erlotinib or afatinib in mouse models of TKI-Naive EGFR L858R-induced lung adenocarcinoma","volume":"22","author":"Pirazzoli","year":"2016","journal-title":"Clin Cancer Res"},{"key":"2025121006534094500_bib46","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.molcel.2019.02.037","article-title":"Gamblers: an antibiotic-induced evolvable cell subpopulation differentiated by reactive-oxygen-induced general stress response","volume":"74","author":"Pribis","year":"2019","journal-title":"Mol Cell"},{"key":"2025121006534094500_bib47","doi-asserted-by":"crossref","first-page":"1024","DOI":"10.1158\/2159-8290.CD-15-0507","article-title":"MYC, metabolism, and cancer","volume":"5","author":"Stine","year":"2015","journal-title":"Cancer Discov"},{"key":"2025121006534094500_bib48","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1096\/fj.06-5730rev","article-title":"DNA precursor metabolism and genomic stability","volume":"20","author":"Mathews","year":"2006","journal-title":"FASEB J"},{"key":"2025121006534094500_bib49","doi-asserted-by":"crossref","first-page":"2464","DOI":"10.1038\/s41388-018-0589-1","article-title":"Cancer stem-like properties and gefitinib resistance are dependent on purine synthetic metabolism mediated by the mitochondrial enzyme MTHFD2","volume":"38","author":"Nishimura","year":"2019","journal-title":"Oncogene"},{"key":"2025121006534094500_bib50","doi-asserted-by":"crossref","first-page":"5712","DOI":"10.1038\/ncomms6712","article-title":"Low MITF\/AXL ratio predicts early resistance to multiple targeted drugs in melanoma","volume":"5","author":"Muller","year":"2014","journal-title":"Nat Commun"},{"key":"2025121006534094500_bib51","doi-asserted-by":"crossref","first-page":"e125341","DOI":"10.1172\/jci.insight.125341","article-title":"Repression of AXL expression by AP-1\/JNK blockage overcomes resistance to PI3Ka therapy","volume":"5","author":"Badarni","year":"2019","journal-title":"JCI Insight"},{"key":"2025121006534094500_bib52","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.ccr.2009.11.022","article-title":"Preexistence and clonal selection of MET amplification in EGFR mutant NSCLC","volume":"17","author":"Turke","year":"2010","journal-title":"Cancer Cell"},{"key":"2025121006534094500_bib53","doi-asserted-by":"crossref","first-page":"4607","DOI":"10.1038\/s41467-020-18442-4","article-title":"Transient IGF-1R inhibition combined with osimertinib eradicates AXL-low expressing EGFR mutated lung cancer","volume":"11","author":"Wang","year":"2020","journal-title":"Nat Commun"},{"key":"2025121006534094500_bib54","doi-asserted-by":"crossref","first-page":"80","DOI":"10.4161\/fly.19695","article-title":"A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3","volume":"6","author":"Cingolani","year":"2012","journal-title":"Fly (Austin)"},{"key":"2025121006534094500_bib55","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1016\/j.celrep.2019.09.001","article-title":"Activation of oncogenic super-enhancers is coupled with DNA repair by RAD51","volume":"29","author":"Hazan","year":"2019","journal-title":"Cell Rep"},{"key":"2025121006534094500_bib56","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1111\/nph.13852","article-title":"Viral infection of the marine alga Emiliania huxleyi triggers lipidome remodeling and induces the production of highly saturated triacylglycerol","volume":"210","author":"Malitsky","year":"2016","journal-title":"New Phytol"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-22-0111\/3183799\/cd-22-0111.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-22-0111\/3207554\/cd-22-0111.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/12\/11\/2666\/3218186\/2666.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/12\/11\/2666\/3218186\/2666.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T11:53:56Z","timestamp":1765367636000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/12\/11\/2666\/710003\/AXL-and-Error-Prone-DNA-Replication-Confer-Drug"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,27]]},"references-count":56,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2022,7,27]]},"published-print":{"date-parts":[[2022,11,2]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-22-0111","relation":{"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.6549711.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541643.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.c.6549711","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541646.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541649.v1","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541652.v1","asserted-by":"object"}],"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.22541652","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541646","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541643","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.22541649","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.3410\/f.742254553.793597819","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,27]]}}}