Abstract 7378: Using game theory to investigate the therapeutic potential of disrupting tumor-microenvironment interactions

Abstract Cancer is a complex disease involving the interplay of several types of malignant and nonmalignant cells. The growth of tumors and surrounding stromal cells can be modeled as an ecosystem, where populations of cancerous and healthy cells interact and compete for resources. In this work, we have explored the application of game theoretic models of cancer to the design of novel anticancer therapies. Notably, a game theoretic-model of tumor-stromal interactions can capture the impact of interactions between cell types and can be used to investigate frequency-dependent parameters describing the impact of drug action during the initiation and growth of metastatic cancers. Previous studies using game theoretic models to describe cancer have focused on explaining progression patterns of specific tumors with known tumor-stromal interactions. This study takes a more general approach to cancer growth dynamics, modeling cancer as a simple game between healthy and cancer cells. This simplified model is used to make general predictions about cancer progression and the efficacy of treatment strategies. Our work suggests that disruption of beneficial interactions between healthy and cancer cells may be a viable treatment strategy for small tumors and preventing metastasis by ensuring that the healthy cell strategy is evolutionarily stable. The efficacy of treatment strategies that disrupt cancer cell cooperation or tumor-stromal dynamics changes as the cancer cell frequency changes. Our work suggests that drugs that target tumor-stromal cell interactions would need to be combined with other types of treatments to be effective against large tumors. Although based on a simplistic model of cancer initiation and progression, the framework derived here can be extended to the real-world design of experimental anticancer therapeutics, and fundamental analyses of this nature can be of practical utility in setting strategy for Target Product Profile design. Citation Format: Debra Van Egeren, Andrew Chen, Madison Stoddard, Lin Yuan, Arijit Chakravarty. Using game theory to investigate the therapeutic potential of disrupting tumor-microenvironment interactions [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 7378.