A New Paradigm For Anti-Angiogenesis Therapy

Rakesh Jain, PhD, of the Massachusetts General Hospital (MGH) Department of Radiation Oncology is now suggesting another, somewhat paradoxical strategy for anti-angiogenic treatment. He outlines the approach in a commentary published in this month's issue of Nature Medicine. "If we normalize the tumor vasculature before its destruction, we can actually improve the efficiency of current cancer therapies, Jain says.

Jain's insight stems from his laboratory observations over the years. His team of researchers saw that the tumor vasculature is made up of very disorganized and abnormal blood vessels, which make it difficult for blood to flow smoothly and completely into a tumor.

This creates an obstacle for cancer treatments: radiation therapy depends on oxygen delivered from the blood, and chemotherapy depends on drugs delivered by good blood flow. "If we prune the tumor's blood vessels and remodel them to become more normal, we can improve the delivery of drugs and other treatments," says Jain.

Interestingly, Jain's group has found that anti-angiogenic agents seem to be good at this sort of pruning, a fact that researchers previously hadn't realized. "We've found that a number of therapeutics actually improve the efficiency of blood vessels before they destroy them," says Jain.

Jain says the key is to find the appropriate dose and schedule of anti-angiogenic drugs that can complement other treatments. "Taking advantage of this new concept is important in order to get the most out of chemotherapy and radiation," says Jain. Clinical trials based on Jain's paradigm are planned at MGH.

He believes his strategy will optimize conditions so that doctors will be able to administer lower doses of cancer-fighting treatments, thereby sparing patients many of the harmful side effects of these agents.

The Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $300 million and major research centers in AIDS, the neurosciences, cardiovascular research, cancer, cutaneous biology, transplantation biology and photomedicine. In 1994, the MGH joined with Brigham and Women?s Hospital to form Partners HealthCare System, an integrated health care delivery system comprising the two academic medical centers, specialty and community hospitals, a network of physician groups and nonacute and home health services.