The evolution of cancer

In a 1976 article in Science, Peter C. Nowell pronounced that "more research should be directed toward understanding and controlling the evolutionary process in tumors." In the thirty years since, what have we learned? Enter Carl Zimmer, who has written a fascinating article on this very topic in January's issue of Scientific American (He also blogged about it, and there is a podcast of a related interview with him here). Zimmer begins by explaining, in a rather novel way, why cancer is so "successful":

Cancer, in other words, re-creates within our own bodies the evolutionary process that enables animals to adapt to their environment. At the level of organisms, natural selection operates when genetic mutations cause some organisms to have more reproductive success than others; the mutations get “selected” in the sense that they persist and become more common in future generations. In cancer, cells play the role of organisms. Cancer- causing changes to DNA cause some cells to reproduce more effectively than ordinary ones. And even within a single tumor, more adapted cells may outcompete less successful ones. “It’s like Darwinian evolution, except that it happens within one organ,” explains Natalia Komarova of the University of California, Irvine.

Then he introduces some potential reasons why the genes that predispose us to cancer might be propagating in the gene pool. The fact that cancer is so common—and that our defenses against it fall short—suggests that perhaps there are evolutionary reasons for it, Zimmer says. (He does rightly point out, however, that natural selection doesn't care what happens to us when we're old. It favors only for those genes that affect our ability to reproduce.)

First, Zimmer describes a potential link between genes that help protect us against cancer (aptly named tumor-suppressor genes) and aging. Research suggests that, though they are at a heightened risk for cancer, mice lacking a tumor suppressor gene called p16-Ink4a do not age as quickly as mice containing normal copies of the gene:

But losing the p16 gene had an upside. When the mice got old, their cells still behaved as if they were young. In one experiment, the scientists studied older mice, some of which had working p16 genes and some of which did not. They destroyed insulin-producing cells in the pancreases of the animals. The normal rodents could no longer produce insulin and developed fatal diabetes. But the ones without the p16 protein developed only mild diabetes and survived. The progenitors of their insulinproducing cells could still multiply quickly, and they repopulated the pancreas with new cells. The scientists found similar results when they examined cells in the blood and brains of the mice: p16 protected them against cancer but also made them old.

Could a missing (or non-expressing) tumor expressor gene, though bad for us in the cancer sense, actually have the hidden benefit of slowing down the aging process? Who knows—mice aren't the perfect models for humans, but it's a possibility. But that's just the start. Another gene that is highly associated with cancer—some cancer cells can't live without its expression—produces a protein called fatty acid synthase, which (again, as its name suggests) synthesizes certain fatty acids. The gene, scientists have found, has undergone big changes since humans first evolved from mammalian ancestors, and while no one can be certain yet why, there is some evidence that the protein helped us evolve bigger and better brains. In other words, then, a gene that potentially increases cancer risk could have been what essentially made us human in the first place.

And there's more. Sperm that divide more quickly (a natural advantage) may be expressing genes that increase cancer risk; and genes that help fetuses grow in the womb could inadvertantly help cancer cells:

Genes that allow cells to build a better placenta, Crespi and Summers argue, can get hijacked by cancer cells—turned on when they would normally be silent. The ability to stimulate new blood vessel formation and aggressive growth serves a tumor just as it does a placenta. “It’s something naturally liable to be co-opted by cancer cell lineages,” Summers says. “It sets up the opportunity for mutations to create tools for cancer cells to use to take over the body.”

Yet even though activation of these usually quiet genes may make cancers more potent, natural selection may still have favored them because they helped fetuses grow. “You may get selection for a gene variant that helps the fetus get a little more from mom,” Crespi says. “But then, when that kid is 60, it might increase the odds of cancer by a few percent. It’s still going to be selected for because of the strong positive early effects.”

Through these examples, Zimmer suggests that looking at cancer through the lens of evolutionary biology may provide some novel insights. As behavioral ecologist Bernard Crespi says in the article, whereas other science tends to focus on the "how" of cancer, evolutionary biology instead investigates the "why." And that question may have some pretty fascinating—not to mention useful!—answers.