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Does natural selection drive the evolution of cancer?

The dynamics of evolution are fully in play within the environment of a tumor, just as they are in forests and meadows, oceans and streams. This is the view of researchers in an emerging cross-disciplinary field that brings the thinking of ecologists and evolutionary biologists to bear on cancer biology.

Insights from their work may have profound implications for understanding why current cancer therapies often fail and how radically new therapies might be devised.

A review by researchers at The Wistar Institute of current research in this new field, published online November 16, will appear in the December issue of the journal Nature Reviews Cancer.

"A tumor cell population is constantly evolving through natural selection," says Carlo C. Maley, Ph.D., an assistant professor in the Molecular and Cellular Oncogenesis Program at Wistar whose own research focuses on this area. He is senior author on the new review. "The mutations that benefit the survival and reproduction of cells in a tumor are the things that drive it towards malignancy.

"Evolution is also driving therapeutic resistance," Maley adds. "When you apply chemotherapy to a population of tumor cells, you're quite likely to have a resistant mutant somewhere in that population of billions or even trillions of cells. This is the central problem in oncology. The reason we haven't been able to cure cancer is that we're selecting for resistant tumor cells. When we spray a field with pesticide, we select for resistant pests. It's the same idea."

Maley notes that there are three necessary and sufficient conditions for natural selection to occur and that all are met in a population of tumor cells. The first requirement is that there be variation in the population. This variation is evident in tumors, which are a mosaic of many different genetic mutants.

The second condition is that the variation must be heritable. This, too, can be seen within a tumor-cell
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Source:The Wistar Institute


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