{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T08:29:56Z","timestamp":1787646596137,"version":"build-2736575974"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T00:00:00Z","timestamp":1787616000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012131","name":"Department of Science and Technology of Liaoning Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012131","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies. Its poor prognosis is closely related to early invasion, extensive stromal deposition, and a strongly immunosuppressive tumor microenvironment. Mutant KRAS is a major driver of PDAC initiation and progression, but its effects are not limited to cancer-cell proliferation. Increasing evidence indicates that oncogenic RAS signaling also alters the surrounding microenvironment by affecting fibroblast activation, extracellular matrix production, antigen presentation, myeloid-cell infiltration, and inflammatory cytokine signaling. These changes can restrict antitumor immune responses and may contribute to treatment resistance. As direct RAS-targeted agents move into clinical development, their effects on tumor immunity have become increasingly relevant. By integrating RAS-driven stromal and immune remodeling with emerging allele-specific and multi-selective RAS therapies, this Mini Review bridges mechanistic and clinical perspectives that are often discussed separately. This framework highlights the rationale for combining RAS inhibitors with immunotherapy and other microenvironment-targeted treatments.<\/jats:p>","DOI":"10.3389\/fcell.2026.1948028","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T07:57:21Z","timestamp":1787644641000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["RAS signaling and remodeling of the immune microenvironment in pancreatic ductal adenocarcinoma: implications of emerging RAS-targeted therapy"],"prefix":"10.3389","volume":"14","author":[{"given":"Di","family":"Meng","sequence":"first","affiliation":[{"name":"Department of Traditional Chinese Medicine, The First Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pancreatic and Biliary Surgery, The First Hospital of China Medical University","place":["Shenyang, Liaoning, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1186\/s12943-025-02288-9","article-title":"ADT-1004: a first-in-class, oral pan-RAS inhibitor with robust antitumor activity in preclinical models of pancreatic ductal adenocarcinoma","volume":"24","author":"Bandi","year":"2025","journal-title":"Mol. 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