Abstract 7230: A novel platform for identifying therapeutic index in pancreatic cancer

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDA) remains highly aggressive with a mere 12% 5-year survival rate, which underscores the urgent need for improved therapeutic approaches. The current standard of care primarily includes surgery and chemotherapy. However, existing therapies often result in severe side effects and offer limited success. The limitations are not only due to the development of treatment resistance but also due to the killing of normal cells, and as such a low therapeutic index. Targeted therapies aimed at the primary drivers of PDA, such as the KRASG12D mutation or the activated ErbB pathway, have shown promise in providing novel treatment options. We have previously demonstrated that combining targeted therapies, specifically KRASG12D and EGFR inhibitors, results in reduced tumor growth in both human and murine PDA organoid models in vitro. However, less is known about how these targeted therapies affect normal cells. Here, we are using co-cultures of normal pancreas and PDA organoids to create a platform that allows us to identify combinations of targeted therapies that can achieve a higher therapeutic index. Our goal is to identify treatment combinations that allow for the use of lower individual drug dose, while exhibiting enhanced anti-tumor efficacy and minimizing toxicities to normal organoids. This approach holds significant promise for improving patient outcomes and addressing the challenges associated with current PDA treatments. Citation Format: Vasiliki Pantazopoulou, Dannielle Engle. A novel platform for identifying therapeutic index in pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7230.