{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T17:03:16Z","timestamp":1790182996446,"version":"4.1.0"},"reference-count":0,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic ductal adenocarcinoma (PDAC) continues to carry a poor prognosis, and only incremental gains in systemic therapy have been made over the past decade. Because activating KRAS mutations are present in more than 90% of PDAC and serve as the inciting oncogenic driver, RAS has long been a coveted but elusive therapeutic target, historically deemed \"undruggable.\" Allele-specific KRASG12C inhibitors provided the first proof of concept, but G12C mutations account for only about 1% of PDAC, in which G12D, G12V, and G12R predominate. Recent advances in the structural and biochemical understanding of RAS have yielded a rapidly expanding therapeutic landscape, broadly comprising non-G12C allele-specific inhibitors, pan-RAS and pan-KRAS inhibitors, and proteolysis-targeting chimeras. This progress is exemplified by the phase III RASolute-302 trial, in which the RAS(ON) multi-selective tri-complex inhibitor daraxonrasib nearly doubled overall survival versus chemotherapy in previously treated metastatic PDAC (13.2 vs 6.7 months), positioning it to become the first broadly applicable RAS-targeted therapy in this disease. Here we review the biology of RAS, the mechanistic rationale and clinical data behind emerging RAS-directed agents, and the central challenges ahead: targeting different KRAS subtypes, managing distinct toxicities, and overcoming the genetic and non-genetic resistance mechanisms that will require rational combination strategies to translate these gains into durable benefit.<\/jats:p>","DOI":"10.1093\/oncolo\/oyag379","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:01:15Z","timestamp":1790164875000},"source":"Crossref","is-referenced-by-count":0,"title":["Current Landscape of RAS-Targeted Therapy for Pancreatic Cancer"],"prefix":"10.1093","author":[{"given":"Y Linda","family":"Wu","sequence":"first","affiliation":[{"name":"Columbia University Irving Medical Center Division of Hematology and Oncology, , New York, NY"},{"name":"New York Presbyterian Hospital , Herbert Irving Pavilion, New York, NY"},{"name":"Herbert Irving Comprehensive Cancer Center , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Herzberg","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center Division of Hematology and Oncology, , New York, NY"},{"name":"New York Presbyterian Hospital , Herbert Irving Pavilion, New York, NY"},{"name":"Herbert Irving Comprehensive Cancer Center , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gulam A","family":"Manji","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center Division of Hematology and Oncology, , New York, NY"},{"name":"New York Presbyterian Hospital , Herbert Irving Pavilion, New York, NY"},{"name":"Herbert Irving Comprehensive Cancer Center , New York, NY"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,9,23]]},"container-title":["The Oncologist"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag379\/71352883\/oyag379.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article-pdf\/doi\/10.1093\/oncolo\/oyag379\/71352883\/oyag379.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T16:12:46Z","timestamp":1790179966000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/oncolo\/advance-article\/doi\/10.1093\/oncolo\/oyag379\/8832333"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,23]]},"references-count":0,"URL":"https:\/\/doi.org\/10.1093\/oncolo\/oyag379","relation":{},"ISSN":["1083-7159","1549-490X"],"issn-type":[{"value":"1083-7159","type":"print"},{"value":"1549-490X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,23]]},"article-number":"oyag379"}}