Talk Plenary (Thu 22)

Cancer through the eye of evolutionary medicine

Author(s): Greaves M

Summary:

There are two striking examples of somatic cell evolution in humans (and vertebrates in general): the immune system and cancer. In the former, recombinase enzymes target diversification of the immunoglobulin and T cell receptor loci in lymphocytes provides the substrate (>1011 variants) for natural selection by infectious antigenic epitopes. In cancer, stochastic mutational processes drive genetic diversification of clones of cell that under natural selection within complex tissue ecosystems and in response to therapeutic pressure. Starting from a single founder cell, cancer clones evolve over time frames of 1 to 50 years, often in a covert fashion, but the end result is the generation of a robust and weed-like quasi-species of immortal and invasive cells that hijack normal tissue function. In exceptional circumstances, cancer cells transit, parasitic like, individual to individual. Therapy itself inadvertently provides positive selective pressure for the emergence of drug-resistant mutant sub-clones.

Whole genome sequencing reveals the extent of genetic, mutational complexity in cancer and when interrogated at the single cell level, it is clear that cancers have tree-like clonal phylogenies with variegated genetics of sub-clones. Within sub-clones, cells with stem cell properties sustain and propel clonal expansion and provide the cellular units of selection. Cancer’s Darwinian character has substantial implications for prevention, prognosis and treatment.

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