Anti-rejection drug studied as a weapon in the cancer war

A drug that has stirred interest in recent years after San Antonio researchers showed it could extend the lifespan of mice now is being looked at to see if it can prevent some common cancers.

Early evidence is promising for the drug, rapamycin, discovered on Easter Island and first approved as an anti-rejection drug for transplant patients.

Last month, the National Cancer Institute awarded a special two-year, $450,000 grant to Dr. Tyler Curiel, an immunologist and professor of medicine at the University of Texas Health Science Center, to study whether the drug is priming the immune system to attack and kill cancer cells as soon as they appear.

“Everybody has what's called cancer immune surveillance,” Curiel said. “Everybody's developing small, clinically unapparent cancers every day, but your immune system can destroy them before they become big. It looks like you take rapamycin and that makes your immune system work better, and helps your cancer immune surveillance so you're less likely to get cancer.”

The discovery that rapamycin might prevent several types of cancer came from a large, San Antonio-led study into several aspects of the drug's anti-aging properties.

Curiel found some clues it might involve that early immune response to cancer, and figured out a way to test the hypothesis using specially bred mice lacking two key parts of the immune system.

The NCI awarded him the grant under its new Provocative Questions Initiative, which is aimed at trying to resolve a handful of the most important but hard-to-answer questions in cancer research.

It's designed to fund high-risk projects that normally wouldn't qualify for money under what some scientists say is an overly cautious approach to research grants.

“The Provocative Questions Initiative has allowed us to reflect on some of the important challenges in the field that, if answered, have the potential to greatly advance the field of cancer research,” said Dr. Doug Lowy, deputy director of the NCI, in an email.

“The fundamental question that needs to be addressed is, does rapamycin prevent cancer through an immune mechanism, yes or no?” Curiel said. “If the answer is really no, then I and others can stop worrying about that aspect of rapamycin and put our efforts somewhere else. If the answer is yes — and the NCI in fact bet a half-million bucks that the answer is going to be yes — then the next question really is, how?”

Rapamycin works by mimicking what happens when mice eat less, targeting a nutrient-sensing pathway in the cell called mTORC. And while eating less is shown to extend a mouse's lifespan, a study published in August found it failed to do the same in monkeys — casting doubt on similar anti-aging effects in people. Curiel thinks the anti-cancer properties may be universal.

And rapamycin is not without side effects. Although it extended the lives of mice, it also left them resistant to insulin — raising fears of diabetes. Earlier this year, scientists discovered a different target in the cell that caused the insulin resistance, raising hopes the drug could be altered to block that unwanted effect.