{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:04:58Z","timestamp":1788458698195,"version":"build-2803163510"},"reference-count":45,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"24","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["1R01CA300245"],"award-info":[{"award-number":["1R01CA300245"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA184984"],"award-info":[{"award-number":["R01CA184984"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100011746","name":"California Institute for Quantitative Biosciences","doi-asserted-by":"publisher","award":["QB3 Postdoctoral Entrepreneurial Fellowship"],"award-info":[{"award-number":["QB3 Postdoctoral Entrepreneurial Fellowship"]}],"id":[{"id":"10.13039\/100011746","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014599","name":"Mark Foundation For Cancer Research","doi-asserted-by":"publisher","award":["ASPIRE II"],"award-info":[{"award-number":["ASPIRE II"]}],"id":[{"id":"10.13039\/100014599","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,6,12]]},"abstract":"<jats:p>\n                    Relapse following targeted therapy remains a central challenge in oncogene-driven cancers. Drug-tolerant persister cells that survive initial treatment without genetic resistance seed relapse, yet despite over a decade of research, no persister-directed therapy has reached clinical approval. To bridge this gap, we developed ResMap, a community resource providing both a standardized experimental framework and quantitative dataset for systematic comparison of persister vulnerabilities across cancer contexts. Using this platform, we evaluated 94 compounds targeting 57 literature-derived candidates in two\n                    <jats:italic toggle=\"yes\">EGFR<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic toggle=\"yes\">mut<\/jats:italic>\n                    <\/jats:sup>\n                    and two\n                    <jats:italic toggle=\"yes\">KRAS<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic toggle=\"yes\">G12C<\/jats:italic>\n                    <\/jats:sup>\n                    lung cancer models under normoxic and hypoxic conditions. Initial screening identified 12 targets with conserved anti-persister activity across genotypes and oxygen environments; follow-up validation reproduced 9 of these targets and revealed variable degrees of persister specificity relative to general cytotoxicity. We also identified context-specific vulnerabilities, including KRAS-relevant combination targets, several of which have since been independently reported and\/or advanced to clinical testing. Integration of human cancer cell line essentiality data and adult mouse loss-of-function phenotypes provided a complementary tolerability layer to refine prioritization. ResMap establishes a foundation for coordinated community efforts to accelerate rational persister-directed combination strategies toward the clinic.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aed7476","type":"journal-article","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T17:58:47Z","timestamp":1781287127000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["ResMap: A community resource for systematic mapping of therapy-persistent residual cancer cell dependencies across contexts"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9689-9385","authenticated-orcid":true,"given":"Xiaoxiao","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-0421-3451","authenticated-orcid":true,"given":"Savitha","family":"Gayathri","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kumbier","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heinz","family":"Hammerlindl","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7639-0347","authenticated-orcid":true,"given":"Erin","family":"Ahern","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0052-7537","authenticated-orcid":true,"given":"Lani F.","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9142-0796","authenticated-orcid":true,"given":"Steven J.","family":"Altschuler","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, University of California, San Francisco, CA, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s43018-024-00819-9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms10690"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4040"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2010.02.027"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.10.027"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00815-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13112666"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13051118"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abi7711"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/2767-9764.CRC-24-0389"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2103695"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204619"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00221-0"},{"key":"e_1_3_2_15_2","first-page":"CD-17-0461","article-title":"Suppression of adaptive responses to targeted cancer therapy by transcriptional repression","volume":"8","author":"Rusan M.","year":"2017","unstructured":"M. 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