{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:53:38Z","timestamp":1792115618961,"version":"4.4.0"},"reference-count":99,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T00:00:00Z","timestamp":1632355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016714","name":"University of Sharjah","doi-asserted-by":"publisher","award":["Targeted grant #1801090141-P"],"award-info":[{"award-number":["Targeted grant #1801090141-P"]}],"id":[{"id":"10.13039\/100016714","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MBRU-AlMahmeed Research Award 2019","award":["ALM1914"],"award-info":[{"award-number":["ALM1914"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The most frequent mutated oncogene family in the history of human cancer is the RAS gene family, including NRAS, HRAS, and, most importantly, KRAS. A hallmark of pancreatic cancer, recalcitrant cancer with a very low survival rate, is the prevalence of oncogenic mutations in the KRAS gene. Due to this fact, studying the function of KRAS and the impact of its mutations on the tumor microenvironment (TME) is a priority for understanding pancreatic cancer progression and designing novel therapeutic strategies for the treatment of the dismal disease. Despite some recent enlightening studies, there is still a wide gap in our knowledge regarding the impact of KRAS mutations on different components of the pancreatic TME. In this review, we will present an updated summary of mutant KRAS role in the initiation, progression, and modulation of the TME of pancreatic ductal adenocarcinoma (PDAC). This review will highlight the intriguing link between diabetes mellitus and PDAC, as well as vitamin D as an adjuvant effective therapy via TME modulation of PDAC. We will also discuss different ongoing clinical trials that use KRAS oncogene signaling network as therapeutic targets.<\/jats:p>","DOI":"10.3390\/ijms221910219","type":"journal-article","created":{"date-parts":[[2021,9,23]],"date-time":"2021-09-23T09:59:15Z","timestamp":1632391155000},"page":"10219","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Highlights on the Role of KRAS Mutations in Reshaping the Microenvironment of Pancreatic Adenocarcinoma"],"prefix":"10.3390","volume":"22","author":[{"given":"Shirin","family":"Hafezi","sequence":"first","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9287-7621","authenticated-orcid":false,"given":"Maha","family":"Saber-Ayad","sequence":"additional","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Department of Clinical Sciences, College of Medicine, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-1043","authenticated-orcid":false,"given":"Wael M.","family":"Abdel-Rahman","sequence":"additional","affiliation":[{"name":"Sharjah Institute for Medical Research, University of Sharjah, Sharjah 27272, United Arab Emirates"},{"name":"Department of Medical Laboratory Sciences, College of Health Sciences, University of Sharjah, Sharjah 27272, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.ejca.2015.11.012","article-title":"Targeting KRAS for diagnosis, prognosis, and treatment of pancreatic cancer: Hopes and realities","volume":"54","author":"Bournet","year":"2016","journal-title":"Eur. 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