Abstract IA009: Stem cells, clonal evolution and therapeutic resistance

Abstract

Abstract Cancer stem cells (CSCs) are the units of selection in cancer (Greaves and Maley 2012; Greaves 2013). If they exist. After a first stage of excitement and strong evidence for CSCs in blood cancers, the concept of CSC and their involvement in solid cancers have been subject to much debate. To understand the role of CSC in clonal evolution and treatment resistance, we need a clear understanding of what CSC are. Several attempts have been made by scientists and philosophers, leading to a dichotomous view of normal and cancer stem cells: either they refer to entities or to a plastic cell states. In the first case, CSCs are the units of selection, and they are involved in treatment resistance. The latter case comes instead with a rejection of the CSC model: in case of plasticity, CSCs are neither a privilege unit of selection, nor a target for cancer treatment. In this talk, I will show that this current dichotomous view is misleading and conflates parameters that need to be distinguished if we want to understand what CSCs are and what is their role in clonal evolution and treatment resistance. By deconvoluting these parameters, we can have a much more precise characterization of CSCs. From this characterization, we can make testable predictions about therapeutic resistance and open new avenues on how to think about cancer treatment. Citation Format: Lucie Laplane. Stem cells, clonal evolution and therapeutic resistance [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 IA009.