Evolution of cancer cell populations

Cancer cell populations, and more generally, populations of cells in proliferation, can be considered as populations of living organisms subject to the laws of evolution, firstly because every mitosis is a chance of mutation, and also because, even without mutations, the genetic memory carried in the DNA can make cells able to unmask, in the presence of a changing local environment (drugs, radiation, metabolic changes), the expression of genes that are normally silenced. This is particularly true of cancer cells, that are, through failures in the normal control of gene expression, prominently plastic, i.e., easily able to rapidly change their phenotypes to adapt to a new environment.

Such plasticity is responsible for the high phenotype heterogeneity of cancer cell populations and may explain their potential of induced drug resistance when they face a life-threatening insult, such as high doses of cytotoxic drugs. In the MAMBA team, we study models of reversible drug-induced drug resistance, with the aim to propose new therapeutic strategies in the clinic to overcome treatment resistance, that is still a major pitfall of cancer therapeutics. Our models take their roots in adaptive dynamics, a discipline of mathematics that firstly appeared in mathematical ecology, and has successfully been transposed to the biology of cancer cell populations.

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