The Problem with the Mutation-Centric View of Cancer

Brian Gallagher in Nautilus:

MutantTo better understand and treat cancer, physicians need to stop oversimplifying its causes. Cancer results not solely from genetic mutations but by adapting to and thriving in micro-environments in the body. That’s the point of view of James DeGregori, a professor in the Department of Biochemistry and Molecular Genetics at the University of Colorado School of Medicine. In a recent Cancer Research paper, DeGregori took a trio of researchers—Cristian Tomasetti, Lu Li, and Bert Vogelstein—to task for their assessment of cancer risk. “Cancers,” they wrote in Science, “are caused by mutations that may be inherited, induced by environmental factors, or result from DNA replications errors.” The latter, they concluded “are responsible for two-thirds of the mutations in human cancers.” Their model of cancer risk is “mutation-centric,” DeGregori said in a recent interview with Nautilus. “What I’m arguing is that they’re modeling a risk by not factoring in how the causes of cancer, like aging or smoking, impacts selection for mutations by impacting tissue micro-environments,” he said. “Their assessments of risks will be wrong because they’re basically missing a major important factor.” In our conversation, DeGregori expanded on how a renewed focus on micro-environments and Darwinian evolutionary pressures can benefit cancer research.

How should we study the origins of cancer?

My lab has been researching the origins of cancers for the last 15 to 17 years. We’re trying to understand cancer from an evolutionary viewpoint, understanding how it evolves. A lot of people think about cancer from an evolutionary viewpoint. But what sets us apart is that we’ve really come to understand cancer by the context these cells find themselves in.

What’s an example of such a context?

While other people will think about aging as the time for mutations to cause advantageous events [for cancer] in cells, we see aging as a very different process. It’s not about the time you get mutations—you get many mutations when you’re young. It's the tissue environment for the cells that changes dramatically as we age. Those new tissue environments basically stimulate the evolution. So the evolution isn’t a process that’s limited by the mutation so much as a process that is limited by micro-environment changes.

More here.

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