Tumor Evolution

Many people with cancer have never taken a class in evolutionary biology, but it’s the basic processes of evolution that may guide the course of their treatment—and research into new treatments—more than any other factor. Although chemotherapy and other types of medicines may hold cancer metastases at bay for years, they can’t eradicate many advanced cancers. One key reason is that tumors can resist, or evolve to resist, the drugs that should be able to kill them.

In the development of cancer treatment resistance, there is an analogy with antibiotic resistance,” says Samuel Aparicio of the University of British Columbia in Vancouver, British Columbia. “This can be a problem in the hospital environment, and it can be a problem in cancer treatment. The linking concept is one of evolutionary fitness: that one cell in a collection may out-survive others because it has some sort of advantage.”

Here’s how it works with bacteria: A course of antibiotics might kill most of the harmful bacteria causing an infection. But if a few bacteria survive, as they are especially likely to do if a patient doesn’t complete a course of antibiotics, the surviving “bugs” could contain an inheritable key to eluding the drug intended to kill them. When these bacteria reproduce or proliferate, their offspring inherit their resistance to antibiotics.

We can now get information about which of these various species is, in fact, growing out. That can be a powerful piece of information.

Over longer periods of time—millions and even billions of years—evolutionary forces have also pushed cells to develop detoxifying systems, such as barriers and pumps, that keep out or remove potentially deadly chemicals. That’s useful for cells struggling to survive in a harsh environment, such as a nascent planet Earth, but challenging for researchers trying to get anticancer drugs to accumulate inside tumor cells. And it can be especially frustrating for patients to learn that some particularly wily tumor cells have eluded damage from chemotherapy and found a way to flourish.

But cancer’s evolutionary prowess does not mean the search for cures is hopeless, Aparicio says. By better understanding the genetic changes underpinning tumor evolution, researchers can envision and design treatments for the future. Genomics—the ability to determine the genetic makeup of cancer cells—is key to this understanding.

“We can now get information about which of these various species is, in fact, growing out. That can be a powerful piece of information,” he says.

For example, patients who receive a diagnosis of ductal carcinoma in situ (DCIS), a noninvasive condition, face difficult choices about treatments, all of which carry some risk. Most patients will never develop invasive breast cancer, but some will, and there is currently no way to distinguish between them.

“If we can learn whether a fraction of the tumor cells have already acquired the ability to invade or survive in other parts of the body, then we may be able to learn which early breast cancers are worthy of more aggressive intervention,” Aparicio says.