{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T15:07:08Z","timestamp":1790089628360,"version":"4.0.1"},"reference-count":10,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T00:00:00Z","timestamp":1771286400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is often caused by mutations in multiple genes, including KRAS (activating the Ras-Raf-MEK-ERK pathway). This study evaluated the role of MEK inhibitor (MEKi)\u2013based combinatorial targeted therapies in patients with PDAC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a retrospective\/prospective observational, single-institution study, including 29 patients with metastatic PDAC with KRAS alterations, treated with MEKi therapies between 2022 and 2024.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Ten patients had KRAS G12R (34.5%), ten G12D (34.5%), and nine G12V (31%). The majority of patients received MEKi therapy as third-line and beyond (KRAS G12R\/G12D\/G12V: 60%\/50%\/78%, respectively). Median overall survival from MEKi initiation for KRAS G12R\/G12D\/G12V was 8.2\/5.1\/4.7\u2009months (P\u2009=\u2009.5), respectively, and median progression-free survival was 4.4\/2.3\/1.4\u2009months (P\u2009=\u2009.11). Six (21%) patients discontinued at least one drug in the treatment combination due to toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>MEKi\u2013based combinatorial therapies had modest disease control in patients with KRAS G12R, and minimal disease control in patients with KRAS G12D\/V in the late-line setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyag040","type":"journal-article","created":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T12:21:09Z","timestamp":1771244469000},"source":"Crossref","is-referenced-by-count":0,"title":["MEK inhibitor\u2013based genomically matched combinatorial targeted therapies in metastatic pancreatic adenocarcinoma with\n                    <i>KRAS<\/i>\n                    alterations"],"prefix":"10.1093","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3267-0247","authenticated-orcid":false,"given":"Elizabeth D","family":"Auckley","sequence":"first","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Yohay","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Ying","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8129-0614","authenticated-orcid":false,"given":"Aniko","family":"Szabo","sequence":"additional","affiliation":[{"name":"Data Science Institute, Division of Biostatistics, Medical College of Wisconsin, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquelyn","family":"Wittmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Grahl","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Froedtert Health, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-2855-3278","authenticated-orcid":false,"given":"Mohammed","family":"Aldakkak","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2681-2109","authenticated-orcid":false,"given":"Samih Z","family":"Thalji","sequence":"additional","affiliation":[{"name":"Department of Surgery, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5284-6994","authenticated-orcid":false,"given":"Thomas","family":"McFall","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4110-1214","authenticated-orcid":false,"given":"Razelle","family":"Kurzrock","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"George","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandana","family":"Kamgar","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Hematology and Oncology, Medical College of Wisconsin and the LaBahn Pancreatic Cancer Program, Milwaukee, WI 53226, United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,2,17]]},"reference":[{"key":"2026092210521667500_oyag040-B1","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":"Cancer Genome Atlas Research Network. 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