{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:05:59Z","timestamp":1790139959742,"version":"4.0.1"},"reference-count":107,"publisher":"Elsevier BV","issue":"9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100001784","name":"Pancreatic Cancer Action Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100001784","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020791","name":"Hale Family Center for Pancreatic Cancer Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020791","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["P50CA127003"],"award-info":[{"award-number":["P50CA127003"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA276268"],"award-info":[{"award-number":["R01 CA276268"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA274276"],"award-info":[{"award-number":["U01 CA274276"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Institutes of Health National Cancer Institute","doi-asserted-by":"publisher","award":["K08CA270417"],"award-info":[{"award-number":["K08CA270417"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005979","name":"Lustgarten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005979","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100020487","name":"Break Through Cancer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100020487","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["cell.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Cell Reports"],"published-print":{"date-parts":[[2025,9]]},"DOI":"10.1016\/j.celrep.2025.116191","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T01:25:04Z","timestamp":1755825904000},"page":"116191","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":8,"title":["Integrative genomic identification of therapeutic targets for pancreatic cancer"],"prefix":"10.1016","volume":"44","author":[{"given":"Jimmy A.","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Evans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ananya D.","family":"Jambhale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Shiau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbo W.","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seema","family":"Chugh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin S.","family":"Kapner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Dilly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Smith","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph D.","family":"Mancias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisca","family":"Vazquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harshabad","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William L.","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0701-6203","authenticated-orcid":false,"given":"Andrew J.","family":"Aguirre","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.celrep.2025.116191_bib1","first-page":"17","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J. Clin."},{"key":"10.1016\/j.celrep.2025.116191_bib2","doi-asserted-by":"crossref","first-page":"1817","DOI":"10.1056\/NEJMoa1011923","article-title":"FOLFIRINOX versus Gemcitabine for Metastatic Pancreatic Cancer","volume":"364","author":"Conroy","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib3","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMoa1304369","article-title":"Increased Survival in Pancreatic Cancer with nab-Paclitaxel plus Gemcitabine","volume":"369","author":"Von Hoff","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib4","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1038\/s43018-022-00349-2","article-title":"Translational advances in pancreatic ductal adenocarcinoma therapy","volume":"3","author":"Hosein","year":"2022","journal-title":"Nat. Cancer"},{"key":"10.1016\/j.celrep.2025.116191_bib5","doi-asserted-by":"crossref","first-page":"2395","DOI":"10.1056\/NEJMoa1809775","article-title":"FOLFIRINOX or Gemcitabine as Adjuvant Therapy for Pancreatic Cancer","volume":"379","author":"Conroy","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib6","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/s41591-022-01717-2","article-title":"Delivering precision oncology to patients with cancer","volume":"28","author":"Mateo","year":"2022","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1200\/JCO.2008.18.9514","article-title":"Oral mTOR inhibitor everolimus in patients with gemcitabine-refractory metastatic pancreatic cancer","volume":"27","author":"Wolpin","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib8","doi-asserted-by":"crossref","first-page":"1923","DOI":"10.1093\/annonc\/mdv264","article-title":"A phase II\/III randomized study to compare the efficacy and safety of rigosertib plus gemcitabine versus gemcitabine alone in patients with previously untreated metastatic pancreatic cancer","volume":"26","author":"O\u2019Neil","year":"2015","journal-title":"Ann. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib9","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1200\/JCO.2017.72.6463","article-title":"CONKO-005: Adjuvant Chemotherapy With Gemcitabine Plus Erlotinib Versus Gemcitabine Alone in Patients After R0 Resection of Pancreatic Cancer: A Multicenter Randomized Phase III Trial","volume":"35","author":"Sinn","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib10","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0140-6736(16)00141-0","article-title":"Pancreatic cancer","volume":"388","author":"Kamisawa","year":"2016","journal-title":"Lancet Lond. Engl."},{"key":"10.1016\/j.celrep.2025.116191_bib11","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1056\/NEJMoa2204619","article-title":"Adagrasib in Non\u2013Small-Cell Lung Cancer Harboring a KRASG12C Mutation","volume":"387","author":"J\u00e4nne","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib12","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa1917239","article-title":"KRASG12C Inhibition with Sotorasib in Advanced Solid Tumors","volume":"383","author":"Hong","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib13","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1056\/NEJMoa2208470","article-title":"Sotorasib in KRAS p.G12C\u2013Mutated Advanced Pancreatic Cancer","volume":"388","author":"Strickler","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib14","doi-asserted-by":"crossref","first-page":"4097","DOI":"10.1200\/JCO.23.00434","article-title":"Adagrasib in Advanced Solid Tumors Harboring a KRASG12C Mutation","volume":"41","author":"Bekaii-Saab","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib15","doi-asserted-by":"crossref","first-page":"994","DOI":"10.1158\/2159-8290.CD-24-0027","article-title":"Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers","volume":"14","author":"Jiang","year":"2024","journal-title":"Cancer Discov."},{"key":"10.1016\/j.celrep.2025.116191_bib16","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41586-023-06123-3","article-title":"Pan-KRAS inhibitor disables oncogenic signalling and tumour growth","volume":"619","author":"Kim","year":"2023","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib17","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1038\/s41586-024-07205-6","article-title":"Concurrent inhibition of oncogenic and wild-type RAS-GTP for cancer therapy","volume":"629","author":"Holderfield","year":"2024","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib18","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1056\/NEJMoa2105281","article-title":"Acquired Resistance to KRASG12C Inhibition in Cancer","volume":"384","author":"Awad","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib19","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41586-021-04065-2","article-title":"Diverse alterations associated with resistance to KRAS(G12C) inhibition","volume":"599","author":"Zhao","year":"2021","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib20","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1158\/2159-8290.CD-25-0349","article-title":"Response and Resistance to RAS Inhibition in Cancer","volume":"15","author":"Ebright","year":"2025","journal-title":"Cancer Discov."},{"key":"10.1016\/j.celrep.2025.116191_bib21","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1038\/nature14169","article-title":"Whole genomes redefine the mutational landscape of pancreatic cancer","volume":"518","author":"Waddell","year":"2015","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib22","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1038\/s41586-019-1102-x","article-title":"WRN helicase is a synthetic lethal target in microsatellite unstable cancers","volume":"568","author":"Chan","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib23","doi-asserted-by":"crossref","first-page":"1214","DOI":"10.1126\/science.aad5214","article-title":"MTAP deletion confers enhanced dependency on the PRMT5 arginine methyltransferase in cancer cells","volume":"351","author":"Kryukov","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.116191_bib24","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1126\/science.aad5944","article-title":"Disordered methionine metabolism in MTAP\/CDKN2A-deleted cancers leads to dependence on PRMT5","volume":"351","author":"Mavrakis","year":"2016","journal-title":"Science"},{"key":"10.1016\/j.celrep.2025.116191_bib25","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2020.108493","article-title":"Synthetic Lethal Interaction between the ESCRT Paralog Enzymes VPS4A and VPS4B in Cancers Harboring Loss of Chromosome 18q or 16q","volume":"33","author":"Neggers","year":"2020","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.116191_bib26","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/j.trecan.2015.10.002","article-title":"Collateral Lethality: A new therapeutic strategy in oncology","volume":"1","author":"Muller","year":"2015","journal-title":"Trends Cancer"},{"key":"10.1016\/j.celrep.2025.116191_bib27","doi-asserted-by":"crossref","first-page":"2412","DOI":"10.1158\/2159-8290.CD-23-0669","article-title":"MRTX1719 Is an MTA-Cooperative PRMT5 Inhibitor That Exhibits Synthetic Lethality in Preclinical Models and Patients with MTAP-Deleted Cancer","volume":"13","author":"Engstrom","year":"2023","journal-title":"Cancer Discov."},{"key":"10.1016\/j.celrep.2025.116191_bib28","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.ccell.2020.12.010","article-title":"MAT2A Inhibition Blocks the Growth of MTAP-Deleted Cancer Cells by Reducing PRMT5-Dependent mRNA Splicing and Inducing DNA Damage","volume":"39","author":"Kalev","year":"2021","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib29","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/j.cell.2017.07.005","article-title":"Project DRIVE: A Compendium of Cancer Dependencies and Synthetic Lethal Relationships Uncovered by Large-Scale, Deep RNAi Screening","volume":"170","author":"McDonald","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib30","doi-asserted-by":"crossref","DOI":"10.15252\/emmm.201910812","article-title":"Synthetic lethality between VPS4A and VPS4B triggers an inflammatory response in colorectal cancer","volume":"12","author":"Szyma\u0144ska","year":"2020","journal-title":"EMBO Mol. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib31","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1056\/NEJMoa1903387","article-title":"Maintenance Olaparib for Germline BRCA-Mutated Metastatic Pancreatic Cancer","volume":"381","author":"Golan","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib32","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":"10.1016\/j.celrep.2025.116191_bib33","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41571-023-00832-4","article-title":"CAR T cell therapy for patients with solid tumours: key lessons to learn and unlearn","volume":"21","author":"Albelda","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib34","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41571-023-00850-2","article-title":"Exploring the next generation of antibody\u2013drug conjugates","volume":"21","author":"Tsuchikama","year":"2024","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib35","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1038\/s41573-024-00896-6","article-title":"The present and future of bispecific antibodies for cancer therapy","volume":"23","author":"Klein","year":"2024","journal-title":"Nat. Rev. Drug Discov."},{"key":"10.1016\/j.celrep.2025.116191_bib36","doi-asserted-by":"crossref","first-page":"2309","DOI":"10.1016\/j.ymthe.2023.06.006","article-title":"Two cases of severe pulmonary toxicity from highly active mesothelin-directed CAR T cells","volume":"31","author":"Haas","year":"2023","journal-title":"Mol. Ther."},{"key":"10.1016\/j.celrep.2025.116191_bib37","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1056\/NEJMoa1814213","article-title":"Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer","volume":"380","author":"Bardia","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib38","doi-asserted-by":"crossref","first-page":"5577","DOI":"10.1016\/j.cell.2021.09.022","article-title":"Spatially confined sub-tumor microenvironments in pancreatic cancer","volume":"184","author":"Gr\u00fcnwald","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib39","doi-asserted-by":"crossref","first-page":"6119","DOI":"10.1016\/j.cell.2021.11.017","article-title":"Microenvironment drives cell state, plasticity, and drug response in pancreatic cancer","volume":"184","author":"Raghavan","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib40","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1038\/s41575-021-00471-z","article-title":"Single-cell RNA sequencing in pancreatic cancer","volume":"18","author":"Han","year":"2021","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.celrep.2025.116191_bib41","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1158\/0008-5472.CAN-22-3050","article-title":"Spatially Resolved Single-Cell Assessment of Pancreatic Cancer Expression Subtypes Reveals Co-expressor Phenotypes and Extensive Intratumoral Heterogeneity","volume":"83","author":"Williams","year":"2023","journal-title":"Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib42","doi-asserted-by":"crossref","first-page":"571","DOI":"10.4251\/wjgo.v15.i4.571","article-title":"Recent advances in targeted therapy for pancreatic adenocarcinoma","volume":"15","author":"Fang","year":"2023","journal-title":"World J. Gastrointest. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib43","doi-asserted-by":"crossref","DOI":"10.1038\/s41572-019-0111-2","article-title":"Breast cancer","volume":"5","author":"Harbeck","year":"2019","journal-title":"Nat. Rev. Dis. Primers"},{"key":"10.1016\/j.celrep.2025.116191_bib44","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1001\/jama.2018.19323","article-title":"Breast Cancer Treatment: A Review","volume":"321","author":"Waks","year":"2019","journal-title":"JAMA"},{"key":"10.1016\/j.celrep.2025.116191_bib45","doi-asserted-by":"crossref","DOI":"10.1186\/s13059-021-02540-7","article-title":"Chronos: a cell population dynamics model of CRISPR experiments that improves inference of gene fitness effects","volume":"22","author":"Dempster","year":"2021","journal-title":"Genome Biol."},{"key":"10.1016\/j.celrep.2025.116191_bib46","doi-asserted-by":"crossref","first-page":"D985","DOI":"10.1093\/nar\/gkw1055","article-title":"Open Targets: a platform for therapeutic target identification and validation","volume":"45","author":"Koscielny","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"10.1016\/j.celrep.2025.116191_bib47","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.ccell.2020.12.008","article-title":"Targeting pan-essential genes in cancer: Challenges and opportunities","volume":"39","author":"Chang","year":"2021","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib48","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/nature16965","article-title":"Genomic analyses identify molecular subtypes of pancreatic cancer","volume":"531","author":"Bailey","year":"2016","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib49","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.ccell.2017.07.007","article-title":"Integrated Genomic Characterization of Pancreatic Ductal Adenocarcinoma","volume":"32","author":"Raphael","year":"2017","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib50","doi-asserted-by":"crossref","first-page":"4140","DOI":"10.1200\/JCO.2024.42.16_suppl.4140","article-title":"Avutometinib\/defactinib and gemcitabine\/nab-paclitaxel combination in first-line metastatic pancreatic ductal adenocarcinoma: Initial safety and efficacy of phase 1b\/2 study (RAMP 205)","volume":"42","author":"Lim","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib51","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1038\/s41586-019-1186-3","article-title":"Next-generation characterization of the Cancer Cell Line Encyclopedia","volume":"569","author":"Ghandi","year":"2019","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib52","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1038\/s41588-018-0155-3","article-title":"Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer","volume":"50","author":"Viswanathan","year":"2018","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib53","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1016\/j.ccell.2016.04.003","article-title":"Loss of Chromosome 8p Governs Tumor Progression and Drug Response by Altering Lipid Metabolism","volume":"29","author":"Cai","year":"2016","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib54","doi-asserted-by":"crossref","first-page":"1192","DOI":"10.1038\/s41588-022-01141-9","article-title":"Cancer cell states recur across tumor types and form specific interactions with the tumor microenvironment","volume":"54","author":"Barkley","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib55","doi-asserted-by":"crossref","first-page":"1168","DOI":"10.1038\/ng.3398","article-title":"Virtual microdissection identifies distinct tumor- and stroma-specific subtypes of pancreatic ductal adenocarcinoma","volume":"47","author":"Moffitt","year":"2015","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib56","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1038\/s41575-019-0109-y","article-title":"Molecular subtypes of pancreatic cancer","volume":"16","author":"Collisson","year":"2019","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"10.1016\/j.celrep.2025.116191_bib57","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/nm.2344","article-title":"Subtypes of pancreatic ductal adenocarcinoma and their differing responses to therapy","volume":"17","author":"Collisson","year":"2011","journal-title":"Nat. Med."},{"key":"10.1016\/j.celrep.2025.116191_bib58","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1158\/1078-0432.CCR-17-2994","article-title":"Genomics-Driven Precision Medicine for Advanced Pancreatic Cancer: Early Results from the COMPASS Trial","volume":"24","author":"Aung","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib59","doi-asserted-by":"crossref","first-page":"4901","DOI":"10.1158\/1078-0432.CCR-19-3724","article-title":"GATA6 Expression Distinguishes Classical and Basal-like Subtypes in Advanced Pancreatic Cancer","volume":"26","author":"O\u2019Kane","year":"2020","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib60","doi-asserted-by":"crossref","first-page":"4932","DOI":"10.1158\/1078-0432.CCR-24-1164","article-title":"Clinical and Genomic Features of Classical and Basal Transcriptional Subtypes in Pancreatic Cancer","volume":"30","author":"Singh","year":"2024","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib61","doi-asserted-by":"crossref","first-page":"15449","DOI":"10.1073\/pnas.1004900107","article-title":"Core epithelial-to-mesenchymal transition interactome gene-expression signature is associated with claudin-low and metaplastic breast cancer subtypes","volume":"107","author":"Taube","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.celrep.2025.116191_bib62","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0051136","article-title":"Meta-Analysis of Gene Expression Signatures Defining the Epithelial to Mesenchymal Transition during Cancer Progression","volume":"7","author":"Gr\u00f6ger","year":"2012","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2025.116191_bib63","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1158\/1078-0432.CCR-12-1558","article-title":"An epithelial-mesenchymal transition gene signature predicts resistance to EGFR and PI3K inhibitors and identifies Axl as a therapeutic target for overcoming EGFR inhibitor resistance","volume":"19","author":"Byers","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib64","doi-asserted-by":"crossref","first-page":"7358","DOI":"10.1021\/bi501250m","article-title":"Distinct properties of the two isoforms of CDP-diacylglycerol synthase","volume":"53","author":"D\u2019Souza","year":"2014","journal-title":"Biochemistry"},{"key":"10.1016\/j.celrep.2025.116191_bib65","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/978-94-007-6331-9_6","article-title":"PtdIns(4,5)P2-mediated cell signaling: emerging principles and PTEN as a paradigm for regulatory mechanism","volume":"991","author":"Gericke","year":"2013","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.celrep.2025.116191_bib66","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.cell.2017.07.029","article-title":"The PI3K Pathway in Human Disease","volume":"170","author":"Fruman","year":"2017","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib67","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.canlet.2010.09.007","article-title":"ZEB1-responsive genes in non-small cell lung cancer","volume":"300","author":"Gemmill","year":"2011","journal-title":"Cancer Lett."},{"key":"10.1016\/j.celrep.2025.116191_bib68","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-04234-2","article-title":"Pan-cancer EMT-signature identifies RBM47 down-regulation during colorectal cancer progression","volume":"7","author":"Rokavec","year":"2017","journal-title":"Sci. Rep."},{"key":"10.1016\/j.celrep.2025.116191_bib69","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2021.108990","article-title":"Stabilized epithelial phenotype of cancer cells in primary tumors leads to increased colonization of liver metastasis in pancreatic cancer","volume":"35","author":"Carstens","year":"2021","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.116191_bib70","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.ccr.2009.03.022","article-title":"A Gene Expression Signature Associated with \u201cK-Ras Addiction\u201d Reveals Regulators of EMT and Tumor Cell Survival","volume":"15","author":"Singh","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib71","doi-asserted-by":"crossref","first-page":"5820","DOI":"10.1158\/0008-5472.CAN-08-2819","article-title":"Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer","volume":"69","author":"Arumugam","year":"2009","journal-title":"Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib72","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1038\/s41588-022-01134-8","article-title":"Single-nucleus and spatial transcriptome profiling of pancreatic cancer identifies multicellular dynamics associated with neoadjuvant treatment","volume":"54","author":"Hwang","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib73","doi-asserted-by":"crossref","DOI":"10.1186\/1476-4598-8-125","article-title":"Intrinsic chemoresistance to gemcitabine is associated with constitutive and laminin-induced phosphorylation of FAK in pancreatic cancer cell lines","volume":"8","author":"Huanwen","year":"2009","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.celrep.2025.116191_bib74","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1158\/2159-8290.CD-24-0177","article-title":"Mechanisms of resistance to oncogenic KRAS inhibition in pancreatic cancer","volume":"14","author":"Dilly","year":"2024","journal-title":"Cancer Discov."},{"key":"10.1016\/j.celrep.2025.116191_bib75","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.celrep.2019.08.090","article-title":"Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers","volume":"29","author":"Sulahian","year":"2019","journal-title":"Cell Rep."},{"key":"10.1016\/j.celrep.2025.116191_bib76","doi-asserted-by":"crossref","first-page":"2532","DOI":"10.1038\/s41467-019-10367-x","article-title":"SHOC2 phosphatase-dependent RAF dimerization mediates resistance to MEK inhibition in RAS-mutant cancers","volume":"10","author":"Jones","year":"2019","journal-title":"Nat. Commun."},{"key":"10.1016\/j.celrep.2025.116191_bib77","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/nature13611","article-title":"Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function","volume":"514","author":"Viale","year":"2014","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib78","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1038\/s41571-021-00470-8","article-title":"Unlocking the potential of antibody-drug conjugates for cancer therapy","volume":"18","author":"Drago","year":"2021","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib79","doi-asserted-by":"crossref","first-page":"E10988","DOI":"10.1073\/pnas.1808790115","article-title":"The in silico human surfaceome","volume":"115","author":"Bausch-Fluck","year":"2018","journal-title":"Proc. Natl. Acad. Sci."},{"key":"10.1016\/j.celrep.2025.116191_bib80","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/nature11003","article-title":"The Cancer Cell Line Encyclopedia enables predictive modelling of anticancer drug sensitivity","volume":"483","author":"Barretina","year":"2012","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib81","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1038\/ng.2653","article-title":"The Genotype-Tissue Expression (GTEx) project","volume":"45","year":"2013","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib82","article-title":"First-in-human dose escalation and expansion study of SYSA1801, an antibody-drug conjugate targeting claudin 18.2 in patients with resistant\/refractory solid tumors","volume":"41","author":"Wang","year":"2023","journal-title":"J. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib83","doi-asserted-by":"crossref","first-page":"6052","DOI":"10.1158\/1078-0432.CCR-09-0586","article-title":"CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates","volume":"15","author":"Govindan","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib84","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1158\/1535-7163.MCT-07-0483","article-title":"Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer","volume":"7","author":"Li","year":"2008","journal-title":"Mol. Cancer Ther."},{"key":"10.1016\/j.celrep.2025.116191_bib85","doi-asserted-by":"crossref","first-page":"5031","DOI":"10.1016\/j.cell.2021.08.023","article-title":"Proteogenomic characterization of pancreatic ductal adenocarcinoma","volume":"184","author":"Cao","year":"2021","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib86","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/s41422-019-0195-y","article-title":"Single-cell RNA-seq highlights intra-tumoral heterogeneity and malignant progression in pancreatic ductal adenocarcinoma","volume":"29","author":"Peng","year":"2019","journal-title":"Cell Res."},{"key":"10.1016\/j.celrep.2025.116191_bib87","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1038\/s41588-022-01157-1","article-title":"Spatially restricted drivers and transitional cell populations cooperate with the microenvironment in untreated and chemo-resistant pancreatic cancer","volume":"54","author":"Cui Zhou","year":"2022","journal-title":"Nat. Genet."},{"key":"10.1016\/j.celrep.2025.116191_bib88","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.cell.2020.08.022","article-title":"Single-Cell Analyses Identify Brain Mural Cells Expressing CD19 as Potential Off-Tumor Targets for CAR-T Immunotherapies","volume":"183","author":"Parker","year":"2020","journal-title":"Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib89","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.27041","article-title":"The Human Cell Atlas","volume":"6","author":"Regev","year":"2017","journal-title":"eLife"},{"key":"10.1016\/j.celrep.2025.116191_bib90","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1016\/j.ygyno.2021.09.023","article-title":"An open-label phase I dose-escalation study of the safety and pharmacokinetics of DMUC4064A in patients with platinum-resistant ovarian cancer","volume":"163","author":"Liu","year":"2021","journal-title":"Gynecol. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib91","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1038\/s41586-025-08927-x","article-title":"Spatial mapping of transcriptomic plasticity in metastatic pancreatic cancer","volume":"642","author":"Pei","year":"2025","journal-title":"Nature"},{"key":"10.1016\/j.celrep.2025.116191_bib92","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/nrclinonc.2017.27","article-title":"Drugs that lack single-agent activity: are they worth pursuing in combination?","volume":"14","author":"Gyawali","year":"2017","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib93","doi-asserted-by":"crossref","first-page":"5880","DOI":"10.1158\/1078-0432.CCR-04-0169","article-title":"Thymidylate synthase gene polymorphism predicts toxicity in colorectal cancer patients receiving 5-fluorouracil-based chemotherapy","volume":"10","author":"Lecomte","year":"2004","journal-title":"Clin. Cancer Res. Off. J. Am. Assoc. Cancer Res."},{"key":"10.1016\/j.celrep.2025.116191_bib94","series-title":"FDA Grants Accelerated Approval to Fam-Trastuzumab Deruxtecan-Nxki for Unresectable or Metastatic HER2-Positive Solid Tumors","author":"Research","year":"2024"},{"key":"10.1016\/j.celrep.2025.116191_bib95","doi-asserted-by":"crossref","first-page":"791","DOI":"10.4161\/auto.23785","article-title":"CFLAR\/c-FLIPL: a star in the autophagy, apoptosis and necroptosis alliance","volume":"9","author":"He","year":"2013","journal-title":"Autophagy"},{"key":"10.1016\/j.celrep.2025.116191_bib96","unstructured":"Mirati Therapeutics Inc. (2023). A Phase 1\/2 Multiple Expansion Cohort Trial of MRTX1133 in Patients With Advanced Solid Tumors Harboring a KRAS G12D Mutation. ClinicalTrials.gov Identifier: NCT05737706. Available at: https:\/\/clinicaltrials.gov\/ct2\/show\/NCT05737706."},{"key":"10.1016\/j.celrep.2025.116191_bib97","unstructured":"Revolution Medicines, Inc. (2024). A Multicenter Open-Label Study of RMC-6236 in Patients With Advanced Solid Tumors Harboring Specific Mutations in RAS. ClinicalTrials.gov Identifier: NCT05379985. Available at: https:\/\/clinicaltrials.gov\/study\/NCT05379985."},{"key":"10.1016\/j.celrep.2025.116191_bib98","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1016\/j.ccell.2024.01.012","article-title":"Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer","volume":"42","author":"Tong","year":"2024","journal-title":"Cancer Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib99","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.devcel.2018.05.027","article-title":"EMT subtype influences epithelial plasticity and mode of cell migration","volume":"45","author":"Aiello","year":"2018","journal-title":"Dev. Cell"},{"key":"10.1016\/j.celrep.2025.116191_bib100","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/s41571-019-0297-y","article-title":"Engineering strategies to overcome the current roadblocks in CAR T cell therapy","volume":"17","author":"Rafiq","year":"2020","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"10.1016\/j.celrep.2025.116191_bib101","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1038\/s43018-023-00667-z","article-title":"Additivity predicts the efficacy of most approved combination therapies for advanced cancer","volume":"4","author":"Hwangbo","year":"2023","journal-title":"Nat. Cancer"},{"key":"10.1016\/j.celrep.2025.116191_bib102","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.50036","article-title":"A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity","volume":"8","author":"Palmer","year":"2019","journal-title":"eLife"},{"key":"10.1016\/j.celrep.2025.116191_bib103","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0121314","article-title":"A Mass Spectrometric-Derived Cell Surface Protein Atlas","volume":"10","author":"Bausch-Fluck","year":"2015","journal-title":"PLoS One"},{"key":"10.1016\/j.celrep.2025.116191_bib104","doi-asserted-by":"crossref","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":"10.1016\/j.celrep.2025.116191_bib105","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."},{"key":"10.1016\/j.celrep.2025.116191_bib106","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1038\/nbt.3460","article-title":"High-throughput identification of genotype-specific cancer vulnerabilities in mixtures of barcoded tumor cell lines","volume":"34","author":"Yu","year":"2016","journal-title":"Nat. Biotechnol."},{"key":"10.1016\/j.celrep.2025.116191_bib107","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1038\/nature08822","article-title":"The landscape of somatic copy-number alteration across human cancers","volume":"463","author":"Beroukhim","year":"2010","journal-title":"Nature"}],"container-title":["Cell Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725009623?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2211124725009623?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:35:01Z","timestamp":1790138101000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2211124725009623"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9]]},"references-count":107,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2025,9]]}},"alternative-id":["S2211124725009623"],"URL":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116191","relation":{},"ISSN":["2211-1247"],"issn-type":[{"value":"2211-1247","type":"print"}],"subject":[],"published":{"date-parts":[[2025,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Integrative genomic identification of therapeutic targets for pancreatic cancer","name":"articletitle","label":"Article Title"},{"value":"Cell Reports","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.celrep.2025.116191","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"116191"}}