(141d) A Quantitative Systems Perspective On Cancer, Immunoevasion, and Somatic Evolution

Following from the clinical challenges associated with molecular targeted therapies, there is increasing realization that one should view cancer from an evolutionary perspective [1]. Evolutionary processes, like cancer, have three common traits: heterogeneity, dynamics, and a selective fitness landscape. Mutagens randomly alter the genome of host cells creating a population of cells that contain different somatic mutations. This genomic rearrangement perturbs cellular homeostasis through changing how cells interact with their tissue microenvironment. Control structures are encoded within cells and organ systems, such as innate and adaptive immunity, to restore cellular homeostasis. These control structures shape the selective fitness landscape and determine whether cells that harbor particular somatic mutations are retained or eliminated from a cell population. While next-generation sequencing has revealed the complexity and heterogeneity of oncogenic transformation, identifying how control structures regulate tissue homeostasis in health and disease is a central challenge in translating our knowledge of biological components into viable therapeutic strategies. In this talk, I will summarize our recent efforts to test postulated intra- and intercellular control structures against the available data using simulation and identify novel mechanisms of cellular cross-talk that cancer cells use to alter the fitness landscape.

References:
1. Klinke DJ. "An evolutionary perspective on anti-tumor immunity" Front Oncol. 2012;2:202.