Abstract A025: Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo

Abstract

Abstract Therapeutic resistance to chemotherapy is frequently the proximate cause of cancer treatment failure and, ultimately, patient mortality. Evolutionary therapies have been developed to address this problem and potentially reduce toxicities. The most successful strategy to date, adaptive therapy (AT), is designed to use chemosensitive cells to out-compete and suppress the chemoresistant cells. However, detailed observations to elucidate the mechanisms of AT's success are lacking. Typically, AT involves lowering the dose of the chemotherapy, thereby reducing toxicity and preserving the immune system. We are evaluating AT for the first time in colorectal cancer, using syngeneic orthotopic xenograft models. This project marks several firsts: 1) sensitive and resistant clones will be tracked longitudinally, 2) AT will be tested with a targeted therapy (MRTX1133), 3) AT will be tested in an immune competent model, 4) multiple drugs will be used for AT, and 5) extinction therapy will be tested in mice. We will employ genetic barcodes and differential luciferase tagging to track the tumor cell subpopulations longitudinally. Currently, we are conducting an in-vivo pilot experiment to validate our protocol, emphasizing tumor engraftment efficacy and tracking cell subpopulations. Additionally, we are investigating the potential of Lactobacillus acidophilus to inhibit tumor growth, augment chemotherapy, and bolster immune response in colorectal cancer. Citation Format: Harley I. Richker, Gissel Marquez-Alcaraz, Carlo Maley. Adaptive therapy: Leveraging evolutionary dynamics for colorectal cancer management in vivo [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Translating Cancer Evolution and Data Science: The Next Frontier; 2023 Dec 3-6; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_2):Abstract nr A025.