Being Fat Can Make Cancer Drugs Useless—Here's Why

Girl chemo
Alexandra Munoz, 5, who lost her hair due to chemotherapy to treat a malignant brain tumor, undergoes a session of treatment with the help of a nurse in the cancer ward of the Luis Calvo Mackenna Hospital in Santiago, Chile, on October 20, 2014. REUTERS/Rodrigo Garrido

For years, doctors have known that cancer patients who are obese tend to face a more challenging fight against cancer. Now, they may know why: People's fat could be digesting the drugs and preventing them from actually getting to the cancer they're meant to treat.

For children fighting leukemia, "obese kids have about a 50 percent higher relapse rate than non-obese kids," Dr. Steven Mittelman told Newsweek. "It's a pretty big effect." Mittelman is a pediatrician and endocrinologist at the UCLA Mattel Children's Hospital.

But there wasn't an obvious explanation for the difference—no one had ever found a drug that fat cells could absorb and process. And the levels of cancer drugs in the blood of patients who are obese is generally the same as they are in patients at a normal weight.

"It doesn't matter what's going on in the bloodstream. It matters what's going on where the cancer cells are," he said. "If you give the chemotherapy and it kills all the cells in the blood but there are a few cells that are surviving in some fat somewhere, then that's a potential source of relapse."

To be clear: in the study, published in Molecular Cancer Research on Friday morning, Mittelman and his colleagues used a very, very small number of mice. (Molecular Cancer Research is run by the American Association for Cancer Research.) They also used some cells cultured in dishes and some human fat and bone marrow samples to come to this conclusion. They didn't actually test things in living humans, though those experiments are being planned. And they also only tested one particular class of drugs called anthracyclines. Anthracyclines are used to treat a wide variety of cancers, including blood cancers, ovarian cancers and breast cancers.

Finally, Mittelman noted, this may not be the only thing contributing to worse outcomes in cancer patients with a bit of extra pudge. "This is one possible contributor to why overweight people have a worse outcome. I don't think this is the only effect or even the major effect."

But the results do make sense. When Mittelman and his team cultivated cancer cells with fat cells in a dish, they found significantly lower concentrations of the drug than if the cells were cultured without other cells or with non-fat cells.

Fat cells don't just sit there. They're alive, and they've got a job to do in the body. "One thing that fat does is it makes estrogen," Mittelman said. Fat has enzymes that help them do things like that, and those same enzymes might be responsible for transforming powerful cancer drugs into a chemical that is far, far less useful. "Clearly we didn't evolve to metabolize chemotherapy," he noted.

That metabolite may have harmful effects of its own. There is some evidence that survivors of cancer who are obese also have higher incidences of heart damage after treatment, he noted, but the literature is too sparse to make the link for sure.