Abstract PO-007: PRMT5 inhibition sensitizes pancreatic cancer to gemcitabine in orthotopic and metastatic murine models

Purpose: The purpose of this study was to investigate protein arginine methyltransferase 5 (PRMT5) as a therapeutic target in combination with gemcitabine for pancreatic cancer in preclinical models. Procedures: In an orthotopic xenograft model, PRMT5 wild-type (WT) or knockout (KO) mPanc96 cells were injected into the pancreata of athymic nude mice. Mice were randomized to control or gemcitabine (100 mg/kg) arms. Tumor volume was measured with magnetic resonance imaging (MRI) at 21, 28, and 35 days post-injection. In a liver metastasis model, PRMT5 WT or KO mPanc96 cells were injected into the spleens of athymic nude mice followed by splenectomy after 10 minutes. Mice were randomized to control or gemcitabine (100 mg/kg) arms. Metastatic tumor burden within the liver was measured with in vivo bioluminescence imaging twice weekly for 19 days post-injection. Relative bioluminescence was calculated relative to post-injection day 2. Results: In the orthotopic model, untreated PRMT5 KO tumors exhibited a 46% reduction in tumor volume compared to untreated PRMT5 WT tumors (959 mm−3 vs. 1766 mm−3, p=0.009). Furthermore, gemcitabine-treated PRMT5 KO tumors exhibited a 30% reduction in tumor volume compared to gemcitabine-treated PRMT5 WT tumors (405 mm−3 vs. 579 mm−3, p=0.046). Compared to untreated PRMT5 WT tumors, gemcitabine-treated PRMT5 KO tumors exhibited a 77% reduction in tumor volume (405 mm−3 vs. 1766 mm−3, p= Citation Format: William J. Kane, Sara J. Adair, Sarbajeet Nagdas, Denis Liu, Xiaolong Wei, Mazhar Adli, Todd W. Bauer. PRMT5 inhibition sensitizes pancreatic cancer to gemcitabine in orthotopic and metastatic murine models [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2020 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2020;80(22 Suppl):Abstract nr PO-007.