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How Exercise May Aid Cancer Treatment

In a new study involving mice, aerobic exercise slowed the growth of breast cancer tumors and made the cancer more sensitive to chemotherapy. The results raise the possibility that exercise may change the biology of some malignant tumors, potentially making them easier to treat.

Scientists and clinicians have known for some time that solid tumors can create their own, peculiar ecosystem within the body. As a tumor grows, it sends out biochemical signals that prompt the creation of additional blood vessels to provide the expanding tumor with more oxygen. Oxygen is, of course, important for cell health, including in normal tissue.

But in some tumors, these new blood vessels begin to proliferate so wildly that they create a “jumble and tumble” of tubes that can curl around and choke one another, reducing blood supply and oxygen to the tumor, says Mark W. Dewhirst, the Gustavo S. Montana Professor of Radiation Oncology at Duke University School of Medicine and senior author of the new study.

As a result, the tumor becomes hypoxic; it exists in an environment with little oxygen.

That condition might seem desirable, since it is fundamentally unhealthy for living tissue to be starved of oxygen. But unfortunately, Dr. Dewhirst says, hypoxia also can make tumors relatively impervious to treatment. Chemotherapy drugs and radiation work better in conjunction with oxygen.

“It’s a bad sign from a clinical perspective when a tumor is hypoxic,” Dr. Dewhirst says.

For years, he and his colleagues have been looking for ways to increase oxygen flow to tumors. There have been trials in animals and people of substances that alter the biochemical signals from the tumors and lead to slower, more normal blood vessel growth to the tumor and reduced hypoxia. But the benefits of this approach have so far been fleeting; eventually the blood vessels leading to the tumor tend to overgrow again like untended vines and hypoxia returns.

So Dr. Dewhirst and colleagues from Massachusetts General Hospital in Boston and Memorial Sloan Kettering Cancer Center in New York City began to consider exercise.

Aerobic exercise is known to increase the flow of oxygen-rich blood to tissues. It’s one of the hallmarks of the activity.

So for the new study, which was published this month in The Journal of the National Cancer Institute, the scientists decided to formally test exercise as a means of altering tumor hypoxia. They began by surgically implanting mouse breast cancer cells into female mice. The scientists did not use human cells, because they would have had to dial down the animals’ immune systems to avoid rejection and wanted to be able to observe interactions between exercise and the animals’ normal immune response.

The mice were then divided into groups that either remained sedentary after surgery or ran at will on wheels in their cages.

In both groups, the tumors took hold and grew, but the growth was significantly slower in the runners. Additional testing showed that the blood vessels feeding the tumors in these animals were healthier than in the sedentary mice. As a result, the runners’ tumors were less hypoxic.

Next, using another group of mice with breast cancer, the scientists had a quarter of the animals remain sedentary. Another quarter of the animals ran on wheels. A third group received a standard drug used in chemotherapy treatment of breast cancer while remaining sedentary. And the final group exercised and received the chemotherapy drug.

After 12 days — a lengthy period in the life of an adult mouse — the animals were reassessed. The tumors in the sedentary animals were, as expected, large and hypoxic.

But exercise and chemotherapy each had slowed tumor growth. The group that had exercised had smaller tumors than did the sedentary mice. So did the animals that had received the chemotherapy drug.

However the mice that simultaneously had exercised and received chemotherapy showed the best outcome, with the smallest tumors by a significant margin.

That result suggests, Dr. Dewhirst says, that exercise had made the breast cancer tumors in the mice more amenable to the chemotherapy. By making the tumors less hypoxic — and paradoxically healthier, he says — exercise “also had made those tumors easier to kill.”

At the same time, exercise seems to have fought the tumors independently of the chemotherapy drugs. In the animals that ran but did not receive chemotherapy, Dr. Dewhirst says, the scientists found blood markers indicating a high degree of tumor cell death, although just how exercise was prompting cancer cells to die remains unclear.

Of course, this study was small and involved mice, not people. There is not yet scientific evidence showing that exercise affects tumor biology in people as it did in the mice in this study.

Still, exercise is advisable and generally tolerable for people undergoing cancer treatment, says study co-author Lee W. Jones, an exercise scientist at Memorial Sloan Kettering whose lab creates customized exercise regimens for patients undergoing treatment at the center. The American Cancer Society also recommends exercise to improve the quality of life among cancer survivors. Obviously, though, consult with your physician before starting any program.

Meanwhile, Dr. Dewhirst has begun follow-up mouse experiments using a different type of breast cancer cell that grows more slowly than the cells used in this study and is a better approximation of human breast cancer, he says. He also hopes to study other types of cancerous tumors in future studies.

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