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Rakesh K. Jain, PhD

Opening a Window of Opportunity

Cediranib belongs to a class of drugs called antiangiogenics. Rather than killing the cancer cells, the approach of traditional chemotherapy drugs, antiangiogenics target the abnormal blood vessels that “feed” the cancer. Shutting down the blood supply “starves” the tumor, and it begins to wither. Eventually, though, tumors recruit new blood vessels and the cancer rebounds.

Many other biological processes also go awry, discovered Rakesh K. Jain, PhD, the A. W. Cook Professor of Tumor Biology at Harvard University and Director of the E. L. Steele Laboratory of Tumor Biology in the Department of Radiation Oncology at Massachusetts General Hospital. His studies in model systems showed that a tumor’s blood vessels become increasingly leaky. Fluids ooze out of the vessels, creating high pressure inside the tumor. The pressure pushes fluids out of the tumor, causing brain swelling. The internal pressure also pushes away chemotherapy drugs that need to enter the tumor to work. The vessels become twisted and kinked, causing blood to slow or even flow backward. The malfunctioning vessels also produce low oxygen and high acidity in the tumor, which renders it resistant to chemotherapy and radiation. If these problems could be fixed, a window of opportunity would open during which traditional anti-cancer treatments could be more effective. An engineer turned biologist, Jain wanted to find this window. Using a model system, he discovered that anti angiogenics did more than temporarily shrink tumors: They also straightened the blood vessels and restored blood flow, giving chemotherapy drugs easier access to the cancer cells. They rebalanced oxygen and acidity levels, helping the anti-cancer medications work more effectively. And they closed the leaks, reduced the pressure, and shrank the swelling.

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