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Does natural selection drive the evolution of cancer?

population. When mutant tumor cells divide to replicate, the daughter cells share the same mutations.

The final condition is that the variation has to affect fitness, the survival and reproduction of the cells. All of the characteristics that are considered hallmarks of cancer affect fitness, according to Maley. Among these are that cancer cells no longer heed normal growth inhibition signals in their environment, they no longer require an external signal to divide as healthy cells do, and they are able to suppress a vital set of internal instructions that require cells to self-destruct when their genes are mutated beyond repair. This protective cell-suicide program carried by normal cells is known as apoptosis.

Seeing a tumor in this light opens a window on new therapeutic strategies.

"It's not just a metaphor to say tumor cell populations are evolving," Maley says. "Evolution is going on in the tumor. So let's think about how we might want to influence that evolution. Can we push it down paths that might be more beneficial to us?"

One idea might be to develop new drugs that would act as benign cell boosters. Such drugs would specifically target the more benign cells in a tumor to increase their relative fitness over their malignant neighbors. This would allow the benign cells to outcompete the malignant cells, leading to a less aggressive, less dangerous tumor.

"Another idea we're pursuing is what we call the sucker's gambit," Maley says. "In this case, you try to increase the fitness of chemosensitive cells so that they outcompete any resistant cells that are in the tumor. And then you apply your chemotherapy. So you sucker the tumor into a vulnerable state and then you hit it with your therapy."

In their review, Maley and his coauthors also explored how the ecological ideas of competition, predation, parasitism, and mutualism unfold in tumors. Here again, they found that the concepts from another field
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Source:The Wistar Institute


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