{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:32:59Z","timestamp":1792787579389,"version":"4.5.0"},"reference-count":119,"publisher":"American Association for Cancer Research (AACR)","issue":"2","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":140,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana del Farmaco, Ministero della Salute","doi-asserted-by":"publisher","award":["Ricerca Corrente"],"award-info":[{"award-number":["Ricerca Corrente"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"name":"FPRC, Fondazione Piemontese per la Ricerca sul Cancro","award":["CARESS"],"award-info":[{"award-number":["CARESS"]}]},{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana del Farmaco, Ministero della Salute","doi-asserted-by":"publisher","award":["RF-2021-12372851"],"award-info":[{"award-number":["RF-2021-12372851"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003197","name":"Agenzia Italiana del Farmaco, Ministero della Salute","doi-asserted-by":"publisher","award":["GR-2021-12375316"],"award-info":[{"award-number":["GR-2021-12375316"]}],"id":[{"id":"10.13039\/501100003197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["20697"],"award-info":[{"award-number":["20697"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["30315"],"award-info":[{"award-number":["30315"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["28922"],"award-info":[{"award-number":["28922"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["21091"],"award-info":[{"award-number":["21091"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020581","name":"Fondazione AIRC per la ricerca sul cancro ETS","doi-asserted-by":"publisher","award":["22795"],"award-info":[{"award-number":["22795"]}],"id":[{"id":"10.13039\/100020581","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["724748"],"award-info":[{"award-number":["724748"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","award":["101020342"],"award-info":[{"award-number":["101020342"]}],"id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010677","name":"H2020 Health","doi-asserted-by":"publisher","award":["754923"],"award-info":[{"award-number":["754923"]}],"id":[{"id":"10.13039\/100010677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010666","name":"H2020 Research Infrastructures","doi-asserted-by":"publisher","award":["731105"],"award-info":[{"award-number":["731105"]}],"id":[{"id":"10.13039\/100010666","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021856","name":"Ministero dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PNC0000001"],"award-info":[{"award-number":["PNC0000001"]}],"id":[{"id":"10.13039\/501100021856","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009885","name":"Regione Piemonte","doi-asserted-by":"publisher","award":["SWIch"],"award-info":[{"award-number":["SWIch"]}],"id":[{"id":"10.13039\/501100009885","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020098","name":"Innovative Health Initiative","doi-asserted-by":"publisher","award":["101007937"],"award-info":[{"award-number":["101007937"]}],"id":[{"id":"10.13039\/100020098","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031478","name":"NextGenerationEU","doi-asserted-by":"publisher","award":["2022CHB9BA"],"award-info":[{"award-number":["2022CHB9BA"]}],"id":[{"id":"10.13039\/100031478","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00689"],"award-info":[{"award-number":["PI21\/00689"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["JR 20\/0005"],"award-info":[{"award-number":["JR 20\/0005"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["PI21\/00041"],"award-info":[{"award-number":["PI21\/00041"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002704","name":"Fundaci\u00f3n Cient\u00edfica Asociaci\u00f3n Espa\u00f1ola Contra el C\u00e1ncer","doi-asserted-by":"publisher","award":["GCAEC20030CERV"],"award-info":[{"award-number":["GCAEC20030CERV"]}],"id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100023479","name":"CRIS Cancer Foundation","doi-asserted-by":"publisher","award":["Excellence Programme 19-30"],"award-info":[{"award-number":["Excellence Programme 19-30"]}],"id":[{"id":"10.13039\/501100023479","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,2,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>The combination of 5-fluorouracil and irinotecan (FOLFIRI) remains a standard-of-care treatment for metastatic colorectal cancer (mCRC) yet benefits only about half of patients. Using patient-derived xenografts, we investigated the biological underpinnings of this heterogeneous response. FOLFIRI-resistant models showed transcriptional upregulation of innate immunity and mitochondrial metabolism genes, together with reduced expression of the DNA polymerase POLD1. Sensitive counterparts exhibited a BRCAness-like phenotype with genomic scars of homologous recombination (HR) deficiency, not caused by genetic or epigenetic loss of HR genes but by low abundance of the RAD51 recombinase. In tumoroids, forced RAD51 overexpression attenuated HR deficiency\u2013related scars and chemotherapy-induced damage, whereas HR inhibition through ATM blockade enhanced drug sensitivity. The predictive relevance of key response determinants was validated in clinical samples. This work illuminates functional, nongenetic facets of BRCAness in mCRC and introduces actionable biomarkers and targets, offering prospects to improve clinical decision-making and broaden therapeutic options for chemorefractory patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance:<\/jats:title>\n                    <jats:p>FOLFIRI response biomarkers in mCRC are lacking. Evidence in patient-derived xenografts, tumoroids, and patients shows that chemosensitivity arises from functional relaxation, rather than (epi)genetic inactivation, of the HR DNA repair pathway. Integrative analyses yield a chemopredictive algorithm centered on the expression of the RAD51 recombinase, with potential to refine patient stratification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1158\/2159-8290.cd-24-0556","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T12:56:01Z","timestamp":1758545761000},"page":"270-295","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Molecular and Functional Landscape of Resistance to FOLFIRI Chemotherapy in Metastatic Colorectal Cancer"],"prefix":"10.1158","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2822-8141","authenticated-orcid":false,"given":"Marco","family":"Avolio","sequence":"first","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7580-6584","authenticated-orcid":false,"given":"Simonetta M.","family":"Leto","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4741-0408","authenticated-orcid":false,"given":"Francesco","family":"Sassi","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-6882","authenticated-orcid":false,"given":"Barbara","family":"Lupo","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1066-927X","authenticated-orcid":false,"given":"Elena","family":"Grassi","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3895-5860","authenticated-orcid":false,"given":"Irene","family":"Catalano","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8036-3789","authenticated-orcid":false,"given":"Eugenia R.","family":"Zanella","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8699-2164","authenticated-orcid":false,"given":"Valentina","family":"Vurchio","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6715-1784","authenticated-orcid":false,"given":"Francesca","family":"Cottino","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3613-6682","authenticated-orcid":false,"given":"Petros K.","family":"Tsantoulis","sequence":"additional","affiliation":[{"name":"3Faculty of Medicine, Universit\u00e9 de Gen\u00e8ve, Geneva, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6841-4240","authenticated-orcid":false,"given":"Luca","family":"Lazzari","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2379-5195","authenticated-orcid":false,"given":"Paolo","family":"Luraghi","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4010-8166","authenticated-orcid":false,"given":"Martina","family":"Ferri","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5939-6922","authenticated-orcid":false,"given":"Francesco","family":"Galimi","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6728-5619","authenticated-orcid":false,"given":"Enrico","family":"Berrino","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5738-2351","authenticated-orcid":false,"given":"Sara E.","family":"Bellomo","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4698-8870","authenticated-orcid":false,"given":"Marco","family":"Viviani","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0612-6109","authenticated-orcid":false,"given":"Alberto","family":"Sogari","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."},{"name":"5Department of Oncology, Molecular Biotechnology Center, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7646-0973","authenticated-orcid":false,"given":"Gianluca","family":"Mauri","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."},{"name":"6Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, Milano, Italy."},{"name":"7Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6146-7411","authenticated-orcid":false,"given":"Federica","family":"Tosi","sequence":"additional","affiliation":[{"name":"7Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7258-1463","authenticated-orcid":false,"given":"Federica","family":"Cruciani","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-0409","authenticated-orcid":false,"given":"Andrea","family":"Sartore-Bianchi","sequence":"additional","affiliation":[{"name":"6Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, Milano, Italy."},{"name":"7Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-2846","authenticated-orcid":false,"given":"Salvatore","family":"Siena","sequence":"additional","affiliation":[{"name":"6Department of Oncology and Hemato-Oncology, Universit\u00e0 degli Studi di Milano, Milano, Italy."},{"name":"7Niguarda Cancer Center, Grande Ospedale Metropolitano Niguarda, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2431-2020","authenticated-orcid":false,"given":"Felice","family":"Borghi","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9541-9354","authenticated-orcid":false,"given":"Valter","family":"Torri","sequence":"additional","affiliation":[{"name":"8Mario Negri Institute for Pharmacological Research \u2013 IRCCS, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4653-6324","authenticated-orcid":false,"given":"Elena","family":"\u00c9lez","sequence":"additional","affiliation":[{"name":"9Medical Oncology Department, Vall d\u2019Hebron Hospital Campus, Barcelona, Spain."},{"name":"10Vall d\u2019Hebron Institute of Oncology (VHIO), Barcelona, Spain."},{"name":"11Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2495-8139","authenticated-orcid":false,"given":"Josep","family":"Tabernero","sequence":"additional","affiliation":[{"name":"9Medical Oncology Department, Vall d\u2019Hebron Hospital Campus, Barcelona, Spain."},{"name":"10Vall d\u2019Hebron Institute of Oncology (VHIO), Barcelona, Spain."},{"name":"11Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8742-4734","authenticated-orcid":false,"given":"Maria","family":"Nieva","sequence":"additional","affiliation":[{"name":"12Medical Oncology Department, Hospital del Mar, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1438-2903","authenticated-orcid":false,"given":"Clara","family":"Montagut","sequence":"additional","affiliation":[{"name":"11Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."},{"name":"12Medical Oncology Department, Hospital del Mar, Barcelona, Spain."},{"name":"13Hospital del Mar Research Institute, Barcelona, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4888-1655","authenticated-orcid":false,"given":"Noelia","family":"Tarazona","sequence":"additional","affiliation":[{"name":"11Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."},{"name":"14Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3806-3691","authenticated-orcid":false,"given":"Andr\u00e9s","family":"Cervantes","sequence":"additional","affiliation":[{"name":"11Centro de Investigaci\u00f3n Biom\u00e9dica en Red de C\u00e1ncer (CIBERONC), Madrid, Spain."},{"name":"14Department of Medical Oncology, Hospital Clinico Universitario, INCLIVA Biomedical Research Institute, University of Valencia, Valencia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3281-8643","authenticated-orcid":false,"given":"Sabine","family":"Tejpar","sequence":"additional","affiliation":[{"name":"15Department of Oncology, Katholieke Universiteit Leuven, Leuven, Belgium."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1647-5070","authenticated-orcid":false,"given":"Alberto","family":"Bardelli","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."},{"name":"5Department of Oncology, Molecular Biotechnology Center, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2024-6131","authenticated-orcid":false,"given":"Caterina","family":"Marchi\u00f2","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"16Department of Medical Sciences, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5361-7122","authenticated-orcid":false,"given":"Silvia","family":"Marsoni","sequence":"additional","affiliation":[{"name":"4IFOM ETS - The AIRC Institute of Molecular Oncology, Milano, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8196-7608","authenticated-orcid":false,"given":"Andrea","family":"Bertotti","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6379-3365","authenticated-orcid":false,"given":"Livio","family":"Trusolino","sequence":"additional","affiliation":[{"name":"1Candiolo Cancer Institute \u2013 FPO IRCCS, Torino, Italy."},{"name":"2Department of Oncology, Candiolo Satellite, University of Torino, Torino, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1086","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"2026020910305872100_bib1","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2026020910305872100_bib2","doi-asserted-by":"crossref","first-page":"22","DOI":"10.3390\/jcm7020022","article-title":"Evaluation of colorectal cancer incidence trends in the United States (2000-2014)","volume":"7","author":"Ansa","year":"2018","journal-title":"J Clin Med"},{"key":"2026020910305872100_bib3","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1186\/s12885-018-4265-1","article-title":"Trends in the contemporary incidence of colorectal cancer and patient characteristics in the United Kingdom: a population-based cohort study using the Health Improvement Network","volume":"18","author":"Soriano","year":"2018","journal-title":"BMC Cancer"},{"key":"2026020910305872100_bib4","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1038\/s41698-023-00353-4","article-title":"Survival improvement for patients with metastatic colorectal cancer over twenty years","volume":"7","author":"Zeineddine","year":"2023","journal-title":"NPJ Precis Oncol"},{"key":"2026020910305872100_bib5","doi-asserted-by":"crossref","first-page":"3469","DOI":"10.1200\/JCO.22.02774","article-title":"FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study","volume":"41","author":"Tournigand","year":"2023","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib6","doi-asserted-by":"crossref","first-page":"4298","DOI":"10.1200\/JCO.2001.19.23.4298","article-title":"ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy","volume":"19","author":"Shirota","year":"2001","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib7","doi-asserted-by":"crossref","first-page":"1238","DOI":"10.1038\/bjc.2013.83","article-title":"ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy","volume":"108","author":"Li","year":"2013","journal-title":"Br J Cancer"},{"key":"2026020910305872100_bib8","doi-asserted-by":"crossref","first-page":"2988","DOI":"10.1158\/1078-0432.CCR-18-1221","article-title":"MAVERICC, a randomized, biomarker-stratified, phase II study of mFOLFOX6-bevacizumab versus FOLFIRI-bevacizumab as first-line chemotherapy in metastatic colorectal cancer","volume":"25","author":"Parikh","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2026020910305872100_bib9","doi-asserted-by":"crossref","first-page":"977","DOI":"10.3390\/cancers12040977","article-title":"An explorative analysis of ABCG2\/TOP-1 mRNA expression as a biomarker test for FOLFIRI treatment in stage III colon cancer patients: results from retrospective analyses of the PETACC-3 trial","volume":"12","author":"Stenvang","year":"2020","journal-title":"Cancers (Basel)"},{"key":"2026020910305872100_bib10","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1200\/JCO.2006.07.4187","article-title":"Gene expression signature in advanced colorectal cancer patients select drugs and response for the use of leucovorin, fluorouracil, and irinotecan","volume":"25","author":"Del Rio","year":"2007","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib11","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ejca.2017.02.003","article-title":"Molecular subtypes of metastatic colorectal cancer are associated with patient response to irinotecan-based therapies","volume":"76","author":"Del Rio","year":"2017","journal-title":"Eur J Cancer"},{"key":"2026020910305872100_bib12","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1038\/nrc.2016.140","article-title":"Interrogating open issues in cancer precision medicine with patient-derived xenografts","volume":"17","author":"Byrne","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib13","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/s41571-022-00682-6","article-title":"Towards precision oncology with patient-derived xenografts","volume":"19","author":"Zanella","year":"2022","journal-title":"Nat Rev Clin Oncol"},{"key":"2026020910305872100_bib14","doi-asserted-by":"crossref","first-page":"508","DOI":"10.1158\/2159-8290.CD-11-0109","article-title":"A molecularly annotated platform of patient-derived xenografts (\u201cxenopatients\u201d) identifies HER2 as an effective therapeutic target in cetuximab-resistant colorectal cancer","volume":"1","author":"Bertotti","year":"2011","journal-title":"Cancer Discov"},{"key":"2026020910305872100_bib15","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1038\/nature14969","article-title":"The genomic landscape of response to EGFR blockade in colorectal cancer","volume":"526","author":"Bertotti","year":"2015","journal-title":"Nature"},{"key":"2026020910305872100_bib16","doi-asserted-by":"crossref","first-page":"272ra12","DOI":"10.1126\/scitranslmed.3010445","article-title":"IGF2 is an actionable target that identifies a distinct subpopulation of colorectal cancer patients with marginal response to anti-EGFR therapies","volume":"7","author":"Zanella","year":"2015","journal-title":"Sci Transl Med"},{"key":"2026020910305872100_bib17","doi-asserted-by":"crossref","first-page":"14262","DOI":"10.1038\/ncomms14262","article-title":"Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors","volume":"8","author":"Sch\u00fctte","year":"2017","journal-title":"Nat Commun"},{"key":"2026020910305872100_bib18","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1158\/2159-8290.CD-20-1531","article-title":"Rational treatment of metastatic colorectal cancer: a reverse tale of men, mice, and culture dishes","volume":"11","author":"Avolio","year":"2021","journal-title":"Cancer Discov"},{"key":"2026020910305872100_bib19","doi-asserted-by":"crossref","first-page":"eabm3687","DOI":"10.1126\/scitranslmed.abm3687","article-title":"Phosphoproteomics of patient-derived xenografts identifies targets and markers associated with sensitivity and resistance to EGFR blockade in colorectal cancer","volume":"15","author":"Beekhof","year":"2023","journal-title":"Sci Transl Med"},{"key":"2026020910305872100_bib20","doi-asserted-by":"crossref","first-page":"eaax8313","DOI":"10.1126\/scitranslmed.aax8313","article-title":"Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype","volume":"12","author":"Lupo","year":"2020","journal-title":"Sci Transl Med"},{"key":"2026020910305872100_bib21","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s00280-009-1153-z","article-title":"Preclinical pharmacokinetic\/pharmacodynamic models to predict synergistic effects of co-administered anti-cancer agents","volume":"66","author":"Goteti","year":"2010","journal-title":"Cancer Chemother Pharmacol"},{"key":"2026020910305872100_bib22","doi-asserted-by":"crossref","first-page":"e1010685","DOI":"10.1371\/journal.pcbi.1010685","article-title":"Computational analysis of 5-fluorouracil anti-tumor activity in colon cancer using a mechanistic pharmacokinetic\/pharmacodynamic model","volume":"18","author":"Ma","year":"2022","journal-title":"PLoS Comput Biol"},{"key":"2026020910305872100_bib23","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1200\/JCO.1994.12.6.1291","article-title":"Relationship between fluorouracil systemic exposure and tumor response and patient survival","volume":"12","author":"Milano","year":"1994","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib24","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s00280-021-04255-9","article-title":"Population pharmacokinetic model of irinotecan and its four main metabolites in patients treated with FOLFIRI or FOLFIRINOX regimen","volume":"88","author":"Deyme","year":"2021","journal-title":"Cancer Chemother Pharmacol"},{"key":"2026020910305872100_bib25","doi-asserted-by":"crossref","first-page":"4866","DOI":"10.1200\/JCO.2005.07.113","article-title":"Phase III randomized trial of FOLFIRI versus FOLFOX4 in the treatment of advanced colorectal cancer: a multicenter study of the Gruppo Oncologico Dell\u2019Italia Meridionale","volume":"23","author":"Colucci","year":"2005","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib26","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1200\/JCO.2006.09.0928","article-title":"Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest","volume":"25","author":"Falcone","year":"2007","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib27","doi-asserted-by":"crossref","first-page":"4779","DOI":"10.1200\/JCO.2007.11.3357","article-title":"Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C study","volume":"25","author":"Fuchs","year":"2007","journal-title":"J Clin Oncol"},{"key":"2026020910305872100_bib28","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1038\/s41591-023-02240-8","article-title":"Codon-specific KRAS mutations predict survival benefit of trifluridine\/tipiracil in metastatic colorectal cancer","volume":"29","author":"van de Haar","year":"2023","journal-title":"Nat Med"},{"key":"2026020910305872100_bib29","doi-asserted-by":"crossref","first-page":"1229885","DOI":"10.3389\/fimmu.2023.1229885","article-title":"Lipocalin 2 receptors: facts, fictions, and myths","volume":"14","author":"Schr\u00f6der","year":"2023","journal-title":"Front Immunol"},{"key":"2026020910305872100_bib30","doi-asserted-by":"crossref","first-page":"764","DOI":"10.1136\/gut.2007.141481","article-title":"Secreted enteric antimicrobial activity localises to the mucus surface layer","volume":"57","author":"Meyer-Hoffert","year":"2008","journal-title":"Gut"},{"key":"2026020910305872100_bib31","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1038\/nri3210","article-title":"Interferon-inducible effector mechanisms in cell-autonomous immunity","volume":"12","author":"MacMicking","year":"2012","journal-title":"Nat Rev Immunol"},{"key":"2026020910305872100_bib32","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.ejphar.2017.08.002","article-title":"Targeting calpains: a novel immunomodulatory approach for microbial infections","volume":"814","author":"Kumar","year":"2017","journal-title":"Eur J Pharmacol"},{"key":"2026020910305872100_bib33","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1101\/gr.138347.112","article-title":"A functional methylome map of ulcerative colitis","volume":"22","author":"H\u00e4sler","year":"2012","journal-title":"Genome Res"},{"key":"2026020910305872100_bib34","doi-asserted-by":"crossref","first-page":"e12882","DOI":"10.1111\/sji.12882","article-title":"A comparative review of intelectins","volume":"92","author":"Chen","year":"2020","journal-title":"Scand J Immunol"},{"key":"2026020910305872100_bib35","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1136\/gut.51.2.169","article-title":"Distribution and partial characterisation of IgG Fc binding protein in various mucin producing cells and body fluids","volume":"51","author":"Kobayashi","year":"2002","journal-title":"Gut"},{"key":"2026020910305872100_bib36","doi-asserted-by":"crossref","first-page":"e1004413","DOI":"10.1371\/journal.pgen.1004413","article-title":"Meiosis-specific cohesin component, Stag3 is essential for maintaining centromere chromatid cohesion, and required for DNA repair and synapsis between homologous chromosomes","volume":"10","author":"Hopkins","year":"2014","journal-title":"PLoS Genet"},{"key":"2026020910305872100_bib37","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nrm2455","article-title":"Cancer as an overhealing wound: an old hypothesis revisited","volume":"9","author":"Sch\u00e4fer","year":"2008","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2026020910305872100_bib38","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/nrc2620","article-title":"Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits","volume":"9","author":"Polyak","year":"2009","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib39","doi-asserted-by":"crossref","first-page":"2686","DOI":"10.1111\/jcmm.17279","article-title":"Vestigial-like family member 3 stimulates cell motility by inducing high-mobility group AT-hook 2 expression in cancer cells","volume":"26","author":"Hori","year":"2022","journal-title":"J Cell Mol Med"},{"key":"2026020910305872100_bib40","doi-asserted-by":"crossref","first-page":"111390","DOI":"10.1016\/j.celrep.2022.111390","article-title":"Snail maintains the stem\/progenitor state of skin epithelial cells and carcinomas through the autocrine effect of matricellular protein Mindin","volume":"40","author":"Badarinath","year":"2022","journal-title":"Cell Rep"},{"key":"2026020910305872100_bib41","doi-asserted-by":"crossref","first-page":"274","DOI":"10.21037\/atm-22-757","article-title":"GeneChip expression profiling identified OLFML2A as a potential therapeutic target in TNBC cells","volume":"10","author":"Gao","year":"2022","journal-title":"Ann Transl Med"},{"key":"2026020910305872100_bib42","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1002\/ijc.32107","article-title":"Characterization of the epithelial membrane protein 3 interaction network reveals a potential functional link to mitogenic signal transduction regulation","volume":"145","author":"Christians","year":"2019","journal-title":"Int J Cancer"},{"key":"2026020910305872100_bib43","doi-asserted-by":"crossref","first-page":"2586","DOI":"10.1158\/2159-8290.CD-22-0200","article-title":"Proteogenomic markers of chemotherapy resistance and response in triple-negative breast cancer","volume":"12","author":"Anurag","year":"2022","journal-title":"Cancer Discov"},{"key":"2026020910305872100_bib44","doi-asserted-by":"crossref","first-page":"6369","DOI":"10.1038\/s41388-021-02029-4","article-title":"Epigenetic induction of lipocalin 2 expression drives acquired resistance to 5-fluorouracil in colorectal cancer through integrin \u03b23\/SRC pathway","volume":"40","author":"Zhang","year":"2021","journal-title":"Oncogene"},{"key":"2026020910305872100_bib45","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1002\/ijc.33711","article-title":"Lipocalin 2 expression promotes tumor progression and therapy resistance by inhibiting ferroptosis in colorectal cancer","volume":"149","author":"Chaudhary","year":"2021","journal-title":"Int J Cancer"},{"key":"2026020910305872100_bib46","doi-asserted-by":"crossref","first-page":"822","DOI":"10.4161\/cbt.7.6.5838","article-title":"Altered expression of cell proliferation-related and interferon-stimulated genes in colon cancer cells resistant to SN38","volume":"7","author":"Gongora","year":"2008","journal-title":"Cancer Biol Ther"},{"key":"2026020910305872100_bib47","doi-asserted-by":"crossref","first-page":"e114719","DOI":"10.15252\/embj.2023114719","article-title":"I\u03baB kinase-\u03b1 coordinates BRD4 and JAK\/STAT signaling to subvert DNA damage-based anticancer therapy","volume":"42","author":"Pecharrom\u00e1n","year":"2023","journal-title":"EMBO J"},{"key":"2026020910305872100_bib48","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.canlet.2020.10.006","article-title":"The meiosis-specific cohesin component stromal antigen 3 promotes cell migration and chemotherapeutic resistance in colorectal cancer","volume":"497","author":"Sasaki","year":"2021","journal-title":"Cancer Lett"},{"key":"2026020910305872100_bib49","first-page":"e74","article-title":"E-cadherin in colorectal cancer: relation to chemosensitivity","volume":"18","author":"Druzhkova","year":"2019","journal-title":"Clin Colorectal Cancer"},{"key":"2026020910305872100_bib50","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1177\/09603271211021479","article-title":"Silencing of E-cadherin expression leads to increased chemosensitivity to irinotecan and oxaliplatin in colorectal cancer cell lines","volume":"40","author":"Skarkova","year":"2021","journal-title":"Hum Exp Toxicol"},{"key":"2026020910305872100_bib51","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1186\/s40001-023-01491-y","article-title":"Identifying individualized prognostic signature and unraveling the molecular mechanism of recurrence in early-onset colorectal cancer","volume":"28","author":"Yang","year":"2023","journal-title":"Eur J Med Res"},{"key":"2026020910305872100_bib52","doi-asserted-by":"crossref","first-page":"147","DOI":"10.21037\/jgo-23-833","article-title":"Identification of fatty acid oxidation-related subtypes by integrated analysis of bulk- and single-cell transcriptome profiling in colorectal cancer","volume":"15","author":"Zou","year":"2024","journal-title":"J Gastrointest Oncol"},{"key":"2026020910305872100_bib53","doi-asserted-by":"crossref","first-page":"e1001453","DOI":"10.1371\/journal.pmed.1001453","article-title":"Gene expression classification of colon cancer into molecular subtypes: characterization, validation, and prognostic value","volume":"10","author":"Marisa","year":"2013","journal-title":"PLoS Med"},{"key":"2026020910305872100_bib54","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1016\/S1470-2045(14)70330-4","article-title":"FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial","volume":"15","author":"Heinemann","year":"2014","journal-title":"Lancet Oncol"},{"key":"2026020910305872100_bib55","doi-asserted-by":"crossref","first-page":"1841","DOI":"10.1093\/annonc\/mdf337","article-title":"Irinotecan: mechanisms of tumor resistance and novel strategies for modulating its activity","volume":"13","author":"Xu","year":"2002","journal-title":"Ann Oncol"},{"key":"2026020910305872100_bib56","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1093\/nar\/gkj430","article-title":"Linking uracil base excision repair and 5-fluorouracil toxicity in yeast","volume":"34","author":"Seiple","year":"2006","journal-title":"Nucleic Acids Res"},{"key":"2026020910305872100_bib57","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.tcb.2015.07.009","article-title":"Repair pathway choices and consequences at the double-strand break","volume":"26","author":"Ceccaldi","year":"2016","journal-title":"Trends Cell Biol"},{"key":"2026020910305872100_bib58","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1038\/s41568-022-00535-5","article-title":"Targeting DNA damage response pathways in cancer","volume":"23","author":"Groelly","year":"2023","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib59","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1016\/j.annonc.2020.05.027","article-title":"The DNA damage response pathway as a land of therapeutic opportunities for colorectal cancer","volume":"31","author":"Mauri","year":"2020","journal-title":"Ann Oncol"},{"key":"2026020910305872100_bib60","doi-asserted-by":"crossref","first-page":"3874","DOI":"10.1158\/1078-0432.CCR-22-0875","article-title":"Targeting the DNA damage response pathways and replication stress in colorectal cancer","volume":"28","author":"Durinikova","year":"2022","journal-title":"Clin Cancer Res"},{"key":"2026020910305872100_bib61","doi-asserted-by":"crossref","first-page":"101376","DOI":"10.1016\/j.xcrm.2023.101376","article-title":"Tolerance to colibactin correlates with homologous recombination proficiency and resistance to irinotecan in colorectal cancer cells","volume":"5","author":"Sogari","year":"2024","journal-title":"Cell Rep Med"},{"key":"2026020910305872100_bib62","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1038\/s41571-021-00532-x","article-title":"Understanding and overcoming resistance to PARP inhibitors in cancer therapy","volume":"18","author":"Dias","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"2026020910305872100_bib63","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1016\/j.cell.2017.06.010","article-title":"Defining a cancer dependency map","volume":"170","author":"Tsherniak","year":"2017","journal-title":"Cell"},{"key":"2026020910305872100_bib64","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1038\/s41467-021-21898-7","article-title":"Integrated cross-study datasets of genetic dependencies in cancer","volume":"12","author":"Pacini","year":"2021","journal-title":"Nat Commun"},{"key":"2026020910305872100_bib65","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/nrc.2015.21","article-title":"BRCAness revisited","volume":"16","author":"Lord","year":"2016","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib66","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1038\/ng.3934","article-title":"A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer","volume":"49","author":"Polak","year":"2017","journal-title":"Nat Genet"},{"key":"2026020910305872100_bib67","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/S0968-0004(98)01232-8","article-title":"Role of the human RAD51 protein in homologous recombination and double-stranded-break repair","volume":"23","author":"Baumann","year":"1998","journal-title":"Trends Biochem Sci"},{"key":"2026020910305872100_bib68","doi-asserted-by":"crossref","first-page":"1203","DOI":"10.1093\/annonc\/mdy099","article-title":"RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer","volume":"29","author":"Cruz","year":"2018","journal-title":"Ann Oncol"},{"key":"2026020910305872100_bib69","doi-asserted-by":"crossref","first-page":"e9172","DOI":"10.15252\/emmm.201809172","article-title":"A RAD51 assay feasible in routine tumor samples calls PARP inhibitor response beyond BRCA mutation","volume":"10","author":"Castroviejo-Bermejo","year":"2018","journal-title":"EMBO Mol Med"},{"key":"2026020910305872100_bib70","doi-asserted-by":"crossref","first-page":"e13366","DOI":"10.15252\/emmm.202013366","article-title":"Quantitative imaging of RAD51 expression as a marker of platinum resistance in ovarian cancer","volume":"13","author":"Hoppe","year":"2021","journal-title":"EMBO Mol Med"},{"key":"2026020910305872100_bib71","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1016\/j.annonc.2021.09.003","article-title":"Association of RAD51 with homologous recombination deficiency (HRD) and clinical outcomes in untreated triple-negative breast cancer (TNBC): analysis of the GeparSixto randomized clinical trial","volume":"32","author":"Llop-Guevara","year":"2021","journal-title":"Ann Oncol"},{"key":"2026020910305872100_bib72","doi-asserted-by":"crossref","first-page":"1646","DOI":"10.1158\/0008-5472.CAN-21-2409","article-title":"Preclinical in vivo validation of the RAD51 test for identification of homologous recombination-deficient tumors and patient stratification","volume":"82","author":"Pellegrino","year":"2022","journal-title":"Cancer Res"},{"key":"2026020910305872100_bib73","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/j.ygyno.2023.01.026","article-title":"A RAD51 functional assay as a candidate test for homologous recombination deficiency in ovarian cancer","volume":"171","author":"Blanc-Durand","year":"2023","journal-title":"Gynecol Oncol"},{"key":"2026020910305872100_bib74","doi-asserted-by":"crossref","first-page":"2466","DOI":"10.1158\/1078-0432.CCR-22-3335","article-title":"RAD51 foci as a biomarker predictive of platinum chemotherapy response in ovarian cancer","volume":"29","author":"Compadre","year":"2023","journal-title":"Clin Cancer Res"},{"key":"2026020910305872100_bib75","doi-asserted-by":"crossref","first-page":"2930","DOI":"10.3390\/cancers13122930","article-title":"Regulation of RAD51 at the transcriptional and functional levels: what prospects for cancer therapy?","volume":"13","author":"Orhan","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2026020910305872100_bib76","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1089\/jir.2012.0133","article-title":"The schlafen family of proteins and their regulation by interferons","volume":"33","author":"Mavrommatis","year":"2013","journal-title":"J Interferon Cytokine Res"},{"key":"2026020910305872100_bib77","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.cyto.2018.03.033","article-title":"SOCS-mediated immunomodulation of natural killer cells","volume":"118","author":"Keating","year":"2019","journal-title":"Cytokine"},{"key":"2026020910305872100_bib78","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1038\/nrc2889","article-title":"IAPs: from caspase inhibitors to modulators of NF-kappaB, inflammation and cancer","volume":"10","author":"Gyrd-Hansen","year":"2010","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib79","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s13046-018-0985-y","article-title":"Fusobacterium nucleatum promotes chemoresistance to 5-fluorouracil by upregulation of BIRC3 expression in colorectal cancer","volume":"38","author":"Zhang","year":"2019","journal-title":"J Exp Clin Cancer Res"},{"key":"2026020910305872100_bib80","doi-asserted-by":"crossref","first-page":"22354","DOI":"10.1002\/cam4.6715","article-title":"TTC7B is a new prognostic biomarker in head and neck squamous cell carcinoma linked to immune infiltration and ferroptosis","volume":"12","author":"He","year":"2023","journal-title":"Cancer Med"},{"key":"2026020910305872100_bib81","doi-asserted-by":"crossref","first-page":"1804137","DOI":"10.1155\/2016\/1804137","article-title":"Nicotinamide mononucleotide adenylyl transferase 2: a promising diagnostic and therapeutic target for colorectal cancer","volume":"2016","author":"Cui","year":"2016","journal-title":"Biomed Res Int"},{"key":"2026020910305872100_bib82","doi-asserted-by":"crossref","first-page":"114143","DOI":"10.1016\/j.biopha.2022.114143","article-title":"NMNAT2: an important metabolic enzyme affecting the disease progression","volume":"158","author":"Li","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"2026020910305872100_bib83","doi-asserted-by":"crossref","first-page":"4293","DOI":"10.3390\/ijms24054293","article-title":"NFIXing cancer: the role of NFIX in oxidative stress response and cell fate","volume":"24","author":"Ribeiro","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026020910305872100_bib84","doi-asserted-by":"crossref","first-page":"105375","DOI":"10.1016\/j.archoralbio.2022.105375","article-title":"Development of gene signature and nomogram for diagnosis and prognosis of oral carcinoma","volume":"136","author":"Yang","year":"2022","journal-title":"Arch Oral Biol"},{"key":"2026020910305872100_bib85","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1517\/14728222.2014.945427","article-title":"The role of pancreatic and duodenal homeobox 1 as a therapeutic target in pancreatic cancer","volume":"18","author":"Fendrich","year":"2014","journal-title":"Expert Opin Ther Targets"},{"key":"2026020910305872100_bib86","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s13046-022-02263-y","article-title":"An organoid model of colorectal circulating tumor cells with stem cell features, hybrid EMT state and distinctive therapy response profile","volume":"41","author":"De Angelis","year":"2022","journal-title":"J Exp Clin Cancer Res"},{"key":"2026020910305872100_bib87","doi-asserted-by":"crossref","first-page":"2257538","DOI":"10.1080\/15592294.2023.2257538","article-title":"ATG9A modulated by miR-195-5p can boost the malignant progression of cervical cancer cells","volume":"18","author":"Liu","year":"2023","journal-title":"Epigenetics"},{"key":"2026020910305872100_bib88","doi-asserted-by":"crossref","first-page":"70","DOI":"10.2174\/1566524016666151222144656","article-title":"The plasma microRNA miR-1914* and -1915 suppresses chemoresistant in colorectal cancer patients by down-regulating NFIX","volume":"16","author":"Hu","year":"2016","journal-title":"Curr Mol Med"},{"key":"2026020910305872100_bib89","doi-asserted-by":"crossref","first-page":"101124","DOI":"10.1016\/j.tranon.2021.101124","article-title":"Amplification of RAD54B promotes progression of hepatocellular carcinoma via activating the Wnt\/\u03b2-catenin signaling","volume":"14","author":"Feng","year":"2021","journal-title":"Transl Oncol"},{"key":"2026020910305872100_bib90","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1021\/cb100428c","article-title":"Identification of specific inhibitors of human RAD51 recombinase using high-throughput screening","volume":"6","author":"Huang","year":"2011","journal-title":"ACS Chem Biol"},{"key":"2026020910305872100_bib91","doi-asserted-by":"crossref","first-page":"7347","DOI":"10.1093\/nar\/gks353","article-title":"RI-1: a chemical inhibitor of RAD51 that disrupts homologous recombination in human cells","volume":"40","author":"Budke","year":"2012","journal-title":"Nucleic Acids Res"},{"key":"2026020910305872100_bib92","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.1021\/jm201173g","article-title":"Inhibition of homologous recombination in human cells by targeting RAD51 recombinase","volume":"55","author":"Huang","year":"2012","journal-title":"J Med Chem"},{"key":"2026020910305872100_bib93","doi-asserted-by":"crossref","first-page":"6236","DOI":"10.1073\/pnas.93.13.6236","article-title":"Targeted disruption of the Rad51 gene leads to lethality in embryonic mice","volume":"93","author":"Tsuzuki","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026020910305872100_bib94","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.2147\/OTT.S322297","article-title":"Targeting RAD51-mediated homologous recombination as a treatment for advanced solid and hematologic malignancies: opportunities and challenges ahead","volume":"15","author":"Tsang","year":"2022","journal-title":"Onco Targets Ther"},{"key":"2026020910305872100_bib95","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1038\/nrc1011","article-title":"ATM and related protein kinases: safeguarding genome integrity","volume":"203","author":"Shiloh","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib96","doi-asserted-by":"crossref","first-page":"3154","DOI":"10.1093\/nar\/gkv160","article-title":"Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation","volume":"43","author":"Bakr","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026020910305872100_bib97","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41389-022-00410-w","article-title":"The TIP60-ATM axis regulates replication fork stability in BRCA-deficient cells","volume":"11","author":"Schleicher","year":"2022","journal-title":"Oncogenesis"},{"key":"2026020910305872100_bib98","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.semradonc.2021.09.008","article-title":"Targeting the ATM kinase to enhance the efficacy of radiotherapy and outcomes for cancer patients","volume":"32","author":"Garc\u00eda","year":"2022","journal-title":"Semin Radiat Oncol"},{"key":"2026020910305872100_bib99","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1038\/nm.2999","article-title":"Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth","volume":"19","author":"Bruchard","year":"2013","journal-title":"Nat Med"},{"key":"2026020910305872100_bib100","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1038\/nrclinonc.2017.101","article-title":"The immune contexture in cancer prognosis and treatment","volume":"14","author":"Fridman","year":"2017","journal-title":"Nat Rev Clin Oncol"},{"key":"2026020910305872100_bib101","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/s41568-021-00388-4","article-title":"Tumour fatty acid metabolism in the context of therapy resistance and obesity","volume":"21","author":"Hoy","year":"2021","journal-title":"Nat Rev Cancer"},{"key":"2026020910305872100_bib102","doi-asserted-by":"crossref","first-page":"5525","DOI":"10.3390\/cancers15235525","article-title":"Concordance between three homologous recombination deficiency (HRD) assays in patients with high-grade epithelial ovarian cancer","volume":"15","author":"Fountzilas","year":"2023","journal-title":"Cancers (Basel)"},{"key":"2026020910305872100_bib103","doi-asserted-by":"crossref","first-page":"6159","DOI":"10.1158\/1078-0432.CCR-10-1027","article-title":"A marker of homologous recombination predicts pathologic complete response to neoadjuvant chemotherapy in primary breast cancer","volume":"16","author":"Graeser","year":"2010","journal-title":"Clin Cancer Res"},{"key":"2026020910305872100_bib104","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/s42003-021-02526-y","article-title":"Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response","volume":"4","author":"Petreus","year":"2021","journal-title":"Commun Biol"},{"key":"2026020910305872100_bib105","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1186\/s12885-022-10084-7","article-title":"ATM kinase inhibitor AZD0156 in combination with irinotecan and 5-fluorouracil in preclinical models of colorectal cancer","volume":"22","author":"Davis","year":"2022","journal-title":"BMC Cancer"},{"key":"2026020910305872100_bib106","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1016\/j.gene.2016.06.031","article-title":"POLD1: central mediator of DNA replication and repair, and implication in cancer and other pathologies","volume":"15","author":"Nicolas","year":"2016","journal-title":"Gene"},{"key":"2026020910305872100_bib107","doi-asserted-by":"crossref","first-page":"e62","DOI":"10.1158\/0008-5472.CAN-17-0582","article-title":"PDX-MI: minimal information for patient-derived tumor xenograft models","volume":"77","author":"Meehan","year":"2017","journal-title":"Cancer Res"},{"issue":"suppl 1","key":"2026020910305872100_bib108","doi-asserted-by":"crossref","first-page":"S81","DOI":"10.1007\/s10916-012-9891-6","article-title":"LAS: a software platform to support oncological data management","volume":"36","author":"Baralis","year":"2012","journal-title":"J Med Syst"},{"key":"2026020910305872100_bib109","doi-asserted-by":"crossref","first-page":"eaay2574","DOI":"10.1126\/scitranslmed.aay2574","article-title":"Patient-derived organoids can predict response to chemotherapy in metastatic colorectal cancer patients","volume":"11","author":"Ooft","year":"2019","journal-title":"Sci Transl Med"},{"key":"2026020910305872100_bib110","doi-asserted-by":"crossref","first-page":"7495","DOI":"10.1038\/s41467-024-51909-2","article-title":"XENTURION is a population-level multidimensional resource of xenografts and tumoroids from metastatic colorectal cancer patients","volume":"15","author":"Leto","year":"2024","journal-title":"Nat Commun"},{"key":"2026020910305872100_bib111","doi-asserted-by":"crossref","first-page":"9139","DOI":"10.1038\/s41467-024-53163-y","article-title":"Integrative ensemble modelling of cetuximab sensitivity in colorectal cancer patient-derived xenografts","volume":"15","author":"Perron","year":"2024","journal-title":"Nat Commun"},{"key":"2026020910305872100_bib112","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol"},{"key":"2026020910305872100_bib113","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"2026020910305872100_bib114","first-page":"100141","article-title":"clusterProfiler 4.0: a universal enrichment tool for interpreting omics data","volume":"2","author":"Wu","year":"2021","journal-title":"Innovation (Camb)"},{"key":"2026020910305872100_bib115","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1093\/bioinformatics\/btu684","article-title":"DOSE: an R\/Bioconductor package for disease ontology semantic and enrichment analysis","volume":"31","author":"Yu","year":"2015","journal-title":"Bioinformatics"},{"key":"2026020910305872100_bib116","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026020910305872100_bib117","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1471-2105-14-7","article-title":"GSVA: gene set variation analysis for microarray and RNA-seq data","volume":"14","author":"H\u00e4nzelmann","year":"2013","journal-title":"BMC Bioinformatics"},{"key":"2026020910305872100_bib118","doi-asserted-by":"crossref","first-page":"e47","DOI":"10.1093\/nar\/gkv007","article-title":"Limma powers differential expression analyses for RNA-sequencing and microarray studies","volume":"43","author":"Ritchie","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"2026020910305872100_bib119","doi-asserted-by":"crossref","first-page":"33","DOI":"10.12688\/f1000research.29032.2","article-title":"Sustainable data analysis with Snakemake","volume":"10","author":"M\u00f6lder","year":"2021","journal-title":"F1000Res"}],"container-title":["Cancer Discovery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-24-0556\/3652190\/cd-24-0556.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/doi\/10.1158\/2159-8290.CD-24-0556\/3712299\/cd-24-0556.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/2\/270\/3731749\/cd-24-0556.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article-pdf\/16\/2\/270\/3731749\/cd-24-0556.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T15:31:23Z","timestamp":1770651083000},"score":1,"resource":{"primary":{"URL":"https:\/\/aacrjournals.org\/cancerdiscovery\/article\/16\/2\/270\/772118\/The-Molecular-and-Functional-Landscape-of"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":119,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,9,22]]},"published-print":{"date-parts":[[2026,2,6]]}},"URL":"https:\/\/doi.org\/10.1158\/2159-8290.cd-24-0556","relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.1158\/2159-8290.31276727","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276739","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296548","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296518","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296533","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276790","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296569","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296503","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296557","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276760","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296563","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276772","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296551","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276742","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276730","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276784","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296494","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276766","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276778","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276805","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276748","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296509","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296515","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296527","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296539","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296500","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296512","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296566","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296497","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296524","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276793","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296530","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296542","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276781","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276775","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296491","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276751","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276763","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31296560","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276757","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276802","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276733","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276799","asserted-by":"object"},{"id-type":"doi","id":"10.1158\/2159-8290.31276745","asserted-by":"object"}],"has-preprint":[{"id-type":"doi","id":"10.1158\/2159-8290.c.8295317","asserted-by":"object"}]},"ISSN":["2159-8274","2159-8290"],"issn-type":[{"value":"2159-8274","type":"print"},{"value":"2159-8290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]}}}