A Pill Against Chemo?

By Carl Marziali on February 9, 2010 10:21 AM

The researchers who proposed limited fasting as a protective strategy against chemotherapy now say that existing drugs may be able to do the job without the hardship and risks of fasting.

In a study published online today in the journal Cancer Research, a team led by USC Davis School of Gerontology associate professor Valter Longo reports that mice with reduced expression of a particular gene tolerated chemotherapy much better than normal mice.

In addition, 60 percent of the genetically engineered mice achieved long-term survival (six months or longer) against melanoma, while the other mice with melanoma died either of the disease or of toxic side effects from chemotherapy.

Longo and his co-authors are now testing whether a combination of fasting and suppression of the IGF-I gene (insulin-like growth factor-I) can achieve even better results.

“We think that the combination of pharmacology and fasting can be much more powerful than fasting alone,” Longo said. “Eventually I think we can get better than fasting [with drugs].”

All the studies would have to be replicated in humans. Two clinical trials of fasting in combination with chemotherapy are planned or under way.

Several companies are testing drugs that block the action of IGF-I, Longo said. Those tests aim at slowing cancer growth, but some of the drugs could be tested for protection against chemotherapy, he added.

The protection achieved by suppressing IGF-I is important but not absolute, Longo cautioned.

“Multiple [genetic] pathways are involved. But it’s enough to reduce IGF-I to achieve some of the protective effects of fasting,” Longo said.

Longo first proposed the fasting strategy in a widely covered study two years ago in Proceedings of the National Academy of Sciences (PNAS).

The Cancer Research study advances the previous research in two important ways, according to Longo.

“It gives a genetic pathway for [the mechanism of fasting], and therefore a drug target,” he said.

“It solves the original concern, which was, how do you know you are not also protecting the cancer cell?”

The PNAS study had showed that starved mice could tolerate higher doses of chemotherapy, but it did not track long-term survival of the animals.

The Cancer Research study, besides showing good long-term survival in mice with reduced IGF-I, found that such mice were protected against three out of four common chemotherapy drugs.

The study also found that reduction of IGF-I protected healthy mammalian cells against chemotherapy, but not cancer cells.

Longo stressed that no cancer patient should undertake a fast or any kind of unusual diet without consulting his or her oncologist, as fasting can be dangerous for certain patients.

For more information about the Longo team’s 2008 PNAS study, visit http://uscnews2.usc.edu/newstools/detail.php?recordnum=15032

Longo’s collaborators were lead author Changhan Lee, graduate student of Longo in the USC Davis School of Gerontology; Fernando Safdie, research associate at the USC Davis School; Min Wei, research assistant professor at the USC Davis School; USC Davis School graduate students Federica Madia and Edoardo Parrella; researchers Lizzia Raffaghello and Giovanna Bianchi of the Giannina Gaslini Institute in Genoa, Italy; and Pinchas Cohen, professor and chief of pediatric endocrinology, with David Hwang, associate resident, both of UCLA.

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