The findings give a new boost to an old approach to medical research: generalized medicine. Personalized medicine will come around eventually, Longo says. But in the meantime, he is focused on finding treatments that can work across diseases. "Especially with cancer, we have an opportunity to look at what is common," he says. "What is it that, by definition, all cancer cells will have difficulty doing?" he asks. The fasting research suggests that the answer is adaptation.
As a cancer grows and its cells mutate, they become more specifically adapted to the environment—a tactic that often spell success for the malignancy. But, Longo says, "if you start changing the environment" by fasting, it has more trouble surviving chemo assaults than healthy tissue cells. Cancer cells, at least in breast cancer experiments, seemed to be fighting to stay alive in the starvation–chemo environment by eating up even more energy, which stresses the malignant cells and causes more damage in them.
Mary Helen Barcellos-Hoff, a professor at the New York University Langone Medical Center who was not involved in the new research, wonders if fasting is also having other effects in the body that is making it less hospitable to cancer, say by increasing immune system sensitivity to the cancer or helping to squelch vascularization of tumors. "I really think modifying the microenvironment to make it less permissive is really one of the untapped potentials for future cancer therapies, she says."
But as Longo notes, fasting—for two to three days in mice, which would be the equivalent of four to five days in humans—alters the body in myriad ways. "You look at their blood, everything changes," from the factors that control blood vessel growth to acids, he says. So now he and his team are going back to look for different signs of what is changing the fasting and chemo in hopes of further optimizing the timing and treatments.
From mice to people
The medical research field is strewn with promising cures-turned-casualties that had to be scrapped after showing promise in mice and failing to work in humans. The cancer battleground is one of the most littered. "Unfortunately we can cure cancer in mice, and we have a much harder time in humans," Barcellos-Hoff says.
The new study might help to quell some of the common reservations about promise in people. "One of the thing that's impressive about it is they used so many models of mouse cancer," Barcellos-Hoff says. The researchers tested more than a dozen different types of cancer lines in mice.
The other concern in translating this research to humans is that people with cancer—and especially those already undergoing treatment—have often already lost a substantial amount of weight. So prescribing days without food could be dangerous, especially for those who already have low blood pressure, diabetes or other metabolic conditions.
Most mice in the fasting groups were able to gain their weight back in five days or so. But humans, of course, are very different animals. Small fasting studies in cancer patients—some involving as long as 62 hours without food before treatment and 24 hours without food afterward—so far have produced only small side effects, Longo says, such as fatigue and headaches. And as Barcellos-Hoff notes, "I think humans would be much grouchier after two days without food." But so far the method seems to be relatively well tolerated in small, carefully controlled studies. And "chemotherapy does make you feel really bad," Barcellos-Hoff says. So fasting "is a lot less unpleasant than many of the things cancer patients are subjected to."