Abstract IA007: Outcompeting cancer in the intestine

Abstract

Abstract Cancers develop in a stepwise fashion as mutations in oncogenes and tumor suppressor genes accumulate. The mutations provide the cells in which they occur typically an advantage over the surrounding wild type neighbors, resulting in clonal expansion. Understanding the nature of the competitive benefit of oncogenic cells might result in the identification of targets for prevention of cancer. In particular in individuals affected by hereditary cancer syndromes, in which the initiating mutations are well-described, this is a promising strategy. I will discuss our work on intestinal carcinogenesis and the impact on stem cell properties of mutations associated with familial cancer syndromes affecting the gut. In particular I will discuss how inactivation of the tumor suppressor gene APC, which is affected in individuals suffering from Familial Adenomatous Polyposis (FAP), generates supercompetitor cells that actively suppress their neighbors. As we will see, the uncovered mechanism directly suggests a potent chemopreventive strategy that is currently being tested in a proof-of-concept clinical trial in FAP individuals. Citation Format: Louis Vermeulen. Outcompeting cancer in the intestine [abstract]. In: Proceedings of the AACR Special Conference on the Evolutionary Dynamics in Carcinogenesis and Response to Therapy; 2022 Mar 14-17. Philadelphia (PA): AACR; Cancer Res 2022;82(10 Suppl):Abstract nr IA007.