A pill that protects against chemo side effects?

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© Simon Jarratt/Corbis

While chemotherapy is often a critical component of cancer treatment, its side effects—which can include hair loss, loss of appetite, nausea, vomiting and new infections, among other health problems—are often debilitating and painful. Adding to previous findings suggesting that fasting prior to chemo might help decrease side effects, researchers from the University of Southern California introduced new research this week that may provide hope for chemotherapy patients—in the form of a pill.

Two years ago Dr. Valter Longo and his colleagues at USC published research in mice suggesting that fasting before chemo might protect healthy cells against the ravages of treatment. A study of mice found that, those who had fasted for two days prior to treatment continued to thrive even after chemo, and seldom experienced long-term side effects of weight and energy loss seen in mice who hadn’t fasted. The researchers then tested these findings on human cells in test tubes—with the same results. Healthy human cells fared better after chemo when they had been subjected to a period of starvation beforehand.

Longo, who is an associate professor of gerontology at USC, said his research grew out of observations about the way cells behave in starvation mode. The effect of starvation is to drive cells into “maintenance mode,” which makes them extraordinarily resistant to stress. Longo theorized that, if starvation impacted healthy cells and cancerous cells differently, there might be a way to prompt healthy cells into a sort of hibernation, leaving only the cancerous cells vulnerable to chemo. And his initial research, published in March, 2008 in the Proceedings of the National Academy of Sciences, bore that out.

Yet now, with the study published this week in the journal Cancer Research, Longo and colleagues explore the possibility of further augmenting protection against chemo using gene suppression drugs. Research in mice with melanoma, that were genetically modified to have reduced expression of a particular gene—the insulin-like growth factor I (IGF-I), specifically—were less vulnerable to side effects of chemo, and had better survival rates than mice without this gene suppression. Similarly to the results of the fasting study, the researchers found that IGF-I suppression protected healthy cells from chemo, but not cancerous cells. Additionally, the genetically modified mice were resistant to three out of four types of chemo tested.

Effectively, the researchers say, the findings indicate a genetic route to replicate the effects of fasting with medication—or potentially combine fasting and a drug regime to more thoroughly thwart the side effects of chemo. Of course, the researchers caution that the protective qualities of IGF-I suppression, while broad, weren’t total. Yet, unlike existing drugs that target single side effects of chemo—such as nausea, for example—the promising aspect of a drug to suppress IGF-I is that it could act more broadly to protect healthy cells, and potentially prevent a wider range of side effects.

These initial findings now need to be replicated in humans, of course, and two trials examining the impact of fasting to protect against the side effects of chemo are currently in initial phases. And additional research is being conducted to examine the effects of suppressing IGF-I to potentially slow the growth of cancer, but researchers are hopeful that future studies will examine the impact of IGF-I suppression on chemo side effects as well.

In the meantime, researchers emphasize that these findings are preliminary, and as such patients should be cautious about changing their diet or fasting prior to treatment without consulting their doctors first.