E12 Clonal evolution and tumor heterogeneity

Topic

This model shifts the scale of analysis compared to the previous model, which described the cycle of a single cell: instead of modeling a single cell, it models how the genetic composition of the entire tumor population evolves over time.

This tumor population is not a homogeneous system but rather an ecosystem of competing clones; each clone possesses its own genotype, and consequently, its own net growth rate, death rate in response to treatment, and therapeutic sensitivity.

The physics governing the competition among these clones is the same theory of evolution described by Darwin, applied here to timescales ranging from weeks to years and to populations numbering between one million and one trillion cells.

This evolution of tumor clones follows the same three principles as any evolutionary process: variation—mutations introducing genetic diversity between clones; heredity—the faithful replication of genetic material, transmitting that diversity from a cell to its daughter cells; and selection—the pressure exerted by the tumor's microenvironment, the patient's immune system, or cancer treatment, favoring certain clones over others.

What makes the tumor system unique compared to other systems where evolution operates is that this selection can be drastically intensified by cancer treatment: while natural selection proceeds at a relatively slow pace, cancer treatment can act as a selective pressure far more intense than any found in nature, accelerating the tumor population's evolutionary process well beyond what would occur without such treatment.

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