Abstract 580: A novel drug suppresses pancreatic cancer growth through immunomodulation

Abstract

Abstract Drug repurposing is an effective strategy that is being used to explore new potential treatments for various diseases. In the current study, utilizing drug repurposing approach, we have identified anti-cancer activity of an anti-parasitic compound (MB). We evaluated the anti-cancer activity of MB in pancreatic ductal adenocarcinoma (PDAC). The average IC50 of MB in several human and murine PDAC cells was 4-6µM. The mode of cell death was apoptosis and which was confirmed using Annexin-V assay. Oral administration of MB suppressed tumor growth in both human and murine subcutaneous and orthotopic models at a dose of 5mg/kg. In the syngeneic orthotopic model, MB showed immune modulation wherein it increased infiltration of CD8 T-cells in the tumor microenvironment as compared to control groups. Based on this, we combined MB with anti-PD1 therapy to evaluate the combinatorial effect. Our results showed significant PDAC tumor growth suppression when a combination of MB and anti-PD1 therapy was used in an orthotopic PDAC tumor model. In conclusion, MB has a promising anti-cancer effect against PDAC tumors and we are currently exploring the molecular mechanism of action in PDAC cell lines and also evaluating if MB has any direct effect on immune cell populations. Citation Format: Shreyas Ramchandra Gaikwad, Sanjay K. Srivastava. A novel drug suppresses pancreatic cancer growth through immunomodulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 580.