How to starve a tumor

Calorie-restricted diets are thought to protect against cancer and slow tumor growth, and a new study published in this week's Nature begins to tease out why the measure works for some tumors, and not for others. Chubby, and more cancer prone Image: Gaetan_lee/flickr For almost a century, researchers have known that fasting helps animals live longer and avoid some cancers, "but which type of cancers would be amenable to this approach, from a therapeutic standpoint, is still an open question,"

Written byTia Ghose

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Calorie-restricted diets are thought to protect against cancer and slow tumor growth, and a new study published in this week's Nature begins to tease out why the measure works for some tumors, and not for others.

Chubby, and more cancer prone
Image: Gaetan_lee/flickr

For almost a century, researchers have known that fasting helps animals live longer and avoid some cancers, "but which type of cancers would be amenable to this approach, from a therapeutic standpoint, is still an open question," said Pier Paolo Pandolfi, a cancer geneticist at Harvard Medical School and Beth Israel Deaconess Cancer Center in Boston, Mass., who was not involved in the study. The study is exciting because it is one of the first to start answering that question at the genetic level, he said. A team led by David Sabatini, a Howard Hughes Medical Investigator and molecular biologist at the Whitehead Institute and the Massachusetts Institute of Technology, injected mice with cells from six human cancer cell lines, including breast, colon, brain, and prostate cancers. The team then subjected half the mice to a draconian 40% cut in calories, while the rest ate as much as they liked. "Contrary to what we expected, not all the tumors responded," Sabatini said. Cutting calories slowed growth in only three of the six cell types--breast and colon cancer cells. For the diet-responsive cell lines, tumors in the fasting mice were between two-thirds and a fifth the volume of those in their freely-eating counterparts. To tease out the difference between the diet-responsive and diet-insensitive cancers, they cultured each cell type with different amounts of insulin and insulin growth factor 1 (IGF1) in the growth medium. The cells that responded to calorie reductions flourished with increasing levels of insulin and IGF1, while the diet-insensitive cells "didn't really seem to care much about insulin and IGF1," Sabatini said. The group suspected that the mechanism at play involved a signaling pathway responsible for regulating cell growth, phosphoinositide 3-kinase/ Akt (PI3k/Akt). By scanning the genetic sequence of specific proteins in the PI3K/Akt pathway, they identified mutations in the diet-insensitive cell lines that kept the pathway switched on. That helped the diet-insensitive tumors keep growing, regardless of the amount of insulin they had access to. "This paper ought to stimulate people to look at this in human cancers," said Lew Cantley, a systems biologist at Harvard Medical School and Beth Israel Deaconess Hospital in Boston, Mass., who was not involved in the study. It would be too costly and slow to evaluate the question in the general population, since large numbers of people would have to be followed for about a decade to get results. Furthermore, patients who have already been diagnosed with cancer generally undergo chemotherapy or radiation almost immediately. Asking patients who are already suffering from nausea, weight loss, and other side effects of their treatment to comply with such a stringent diet is not feasible, he said. Instead, one possibility would be to study dietary restriction in people with an elevated risk of cancer, since they wouldn't have to be monitored for as long. People with early-stage prostate cancer, for example, often don't undergo treatment right away, but instead are closely monitored to see if the tumor grows. Women who have had breast cancer would also be good candidates, because they have a higher risk of forming metastases. Even so, Cantley noted, it won't be easy. "The problem is people always cheat on their diet," he said.
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