Scientists at Massachusetts General Hospital (MGH) have discovered powerful anti-angiogenic properties in herceptin, a monoclonal antibody used to fight certain forms of breast cancer. Herceptin is known to block the cell receptor HER2 on breast cancer cells and is used to treat women whose tumors produce extra copies of HER2, a more aggressive form of cancer. The new data show that herceptin also targets multiple factors secreted by cancer cells which maintain the tumor's blood supply. In the March 21 issue of Nature, researchers from the MGH Department of Radiation Oncology show that herceptin can reduce the diameter and volume of tumor blood vessels, slow tumor growth, and prolong survival in animal models of cancer.
"The beauty of this molecule is that it has multiple anti-angiogenic effects and so it acts like a cocktail of angiogenesis-blocking drugs," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology, the report's senior author. Scientists and physicians have been trying for years to block a tumor's ability to secrete factors that create new blood vessels and allow cancer cells to gain access to fresh supplies of blood and oxygen. However, when one of these angiogenic factors is successfully blocked, the cancer cells can adapt and secrete other factors. Jain and his team have found that herceptin can effectively target at least five factors, thereby thwarting a number of the cancer cells' tactics.
The MGH research includes clues that the host -- the body in which a tumor grows -- also plays a role in herceptin's effects. Following herceptin treatments, tumor cells cultured in the laboratory expressed more of certain angiogenic factors and less of others compared with tumors treated in mice. "This shows that we need to understand the host better," says Jain. "We used to think of a tumor as a big bag of cancer cells separate from the host, but now we know that host cells are active participants in cancer progression as well as regression."
Jain sees great promise for herceptin and similar agents in the future. "Someday we may have detailed profiles of individual patients and their tumors, and we'll know which genes and angiogenic factors need to be targeted," he says. "By identifying other antibodies or inhibitors like herceptin, we may be able to tailor treatments through multiple cocktail therapies."
The other members of the MGH research team are Yotaro Izumi, MD, PhD, first author; Lei Xu, MD, PhD; Emmanuelle di Tomaso, PhD; and Dai Fukumura, MD, PhD. The study was supported by research grants from Genentech and the National Cancer Institute.
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.
Journal
Nature