Abstract 13: Aspirin and metformin combination inhibits PDAC progression and metastasis in KPC mice

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that generally escapes detection until it reaches an advanced stage. Hence, developing strategies that inhibit PDAC progression is of utmost importance. Observational studies suggest that frequent use of metformin and aspirin reduces PDAC risk. Since these agents have different mechanisms of action, combining them may lead to additive inhibitory effects on PDAC. Here we aimed to validate the usefulness of the combination of aspirin with metformin in the Ptf1acre-ERTM.LSL-KrasG12D/+. LSL-Trp53R172H/+ (KPC) mouse model. Aspirin (600 ppm or 1,200 ppm) and metformin (500 ppm or 1,000 ppm) either individually or in combination were tested for their effect on pancreatic intraepithelial neoplasia (PanINs), PDAC, and metastasis in KPC mice. Eight week-old KPC mice were administered tamoxifen by gavage to initiate tumorigenesis (PanINs) and randomized to control and experimental groups. Seven weeks later, experimental diets containing test agents individually or in combination were administered to the KPC mice. Mice were euthanized 32 weeks post-tamoxifen administration and pancreata were evaluated. Histological analysis showed 100% penetrance of PanIN lesions in all the KPC mice. Control diet fed mice showed 100% PDAC incidence. Aspirin (1,200 ppm) or metformin (1,000 ppm) showed significant inhibition of PDAC incidence by 15.6% (P Citation Format: Altaf Mohammed, Venkateshwar Madka, Gaurav Kumar, Anil Singh, Nicole Stratton, Stanley Lightfoot, Mark S. Miller, Chinthalapally V. Rao. Aspirin and metformin combination inhibits PDAC progression and metastasis in KPC mice [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 13.