Curbing Chemo: Fasting cushions drug’s side effects in mice

A new study in mice suggests a connection between short-term starvation and the ability to tolerate chemotherapy.

Starving cancer-ridden mice for two days sent the animals’ bodies into a “maintenance mode” that protected their healthy cells from a harsh chemo drug but left cancerous cells vulnerable.

Chemotherapy drugs kill healthy cells as well as cancerous ones, so targeting drugs more narrowly at tumors is a major goal of cancer research. The new study suggests a novel way to protect healthy cells from chemo, but translating the discovery into therapies for people might not be straightforward.

“If just skipping breakfast would make the chemotherapy easier to tolerate that would be great, but we have common clinical experience that tells us that this is not the case,” comments Michael Pollak, a clinical oncologist and researcher at McGill University in Montreal. “We have lots of patients who have poor nutritional status because they’re so sick but who still have poor responses to chemotherapy.”

Because many cancer patients are already undernourished, further starvation could be risky and ill advised, Pollak says. “There are many questions that would have to be addressed before this could be considered for people.” But he says understanding the molecular mechanisms that protect the mice’s healthy cells could lead to drugs that directly trigger those mechanisms without the need for fasting.

A team of researchers led by Valter D. Longo of the University of Southern California in Los Angeles injected mice with human cancer cells and later starved one group of animals for 48 or 60 hours. The researchers then treated both groups of mice with abnormally high doses of etoposide, a common chemotherapy drug. Nearly all of the starved mice survived the initial dose, but about half of the non-starved mice died within a few days, the team reports online March 31 in Proceedings of the National Academy of Sciences.

“It seems that the healthy cells are much more protected” in the starved mice, says research team member Federica Madia, who is also at USC.

Scientists have known since the 1930s that many animals fed an austere diet of about one-third fewer calories live 30 to 50 percent longer. Starving animals every other day has produced similar results in some experiments. The theory goes that a scarcity of food activates ancient repair mechanisms in the animals’ cells, diverting energy from growth and reproduction to help the animals hang on until lean times pass.

Many kinds of cancer cells ignore the signals to switch from growth to repair, so starvation affords them less protection, the researchers say.

“I have what I would call guarded enthusiasm,” comments James M. Harper, who researches aging at the University of Michigan School of Medicine in Ann Arbor. “It’s too early to really hang my hat on it, but there’s a lot of exciting follow-up work to do.”

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