The antitumoral effect of statins in pancreatic ductal adenocarcinoma: a scoping review

IntroductionPancreatic ductal adenocarcinoma (PDAC) remains one of the most aggressive and invasive malignancies, with limited response to the currently available systemic therapy options. Having a 5-year survival of 12%, there is a serious need for novel therapeutic options, including drug repurposing for the treatment of PDAC. In recent years, 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) inhibitors, also known as statins, have been identified as potential candidates for PDAC therapy repurposing.MethodsWe have performed a scoping literature review to summarize the extent of knowledge on statins’ effects on PDAC, both in clinical studies and preclinical models, and to explain the mechanisms underlying statins’ antiproliferative effect on PDAC. We have followed the PRISMA Extension for Scoping Reviews (PRISMA-ScR) guidelines. We have searched PubMed and Web of Science for original articles published between January 2021 and January 2026.ResultsOur review systematically linked the clinical outcomes, molecular mechanism, and tumor microenvironment in PDAC-statin research. Clinical studies of the correlation between statin treatment and PDAC incidence yielded mixed results. Among the mechanisms we have summarized are disruption of the plasma membrane lipid rafts, reduction of protein prenylation, increase of the tumor immunogenicity, reduction of signaling, both RAS-mediated and by alternative pathways, and disruption of mitochondrial respiration. Statins also showed synergistic effects with chemotherapeutic agents including gemcitabine, 5-fluorouracil, and oxaliplatin in preclinical models.DiscussionDespite promising preclinical data, the clinical evidence remains limited to observational studies and a single phase 2 trial. Randomized controlled trials with biomarker-driven patient selection are needed to establish the role of statins as adjuvant therapy in PDAC.