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Rapamycin shown to inhibit angiogenesis

BOSTON Scientists have long known that the blood vessels of tumors differ markedly from normal blood vessels. Now, a research team led by scientists at Beth Israel Deaconess Medical Center (BIDMC) has identified a signaling pathway which, when activated, transforms otherwise healthy blood vessels into the leaky, misshapen vasculature that characterizes cancerous tumors.

The findings, published in the August 2006 issue of Cancer Cell, additionally demonstrate that rapamycin, a compound used for immunosuppression in transplant patients and currently under investigation as a cancer treatment, can successfully block this signaling pathway--known as the Akt pathway-- in blood vessels. This discovery further enhances the drug's promise as a cancer therapy.

"There are three major hallmarks associated with tumor blood vessels," explains the study's senior author Laura Benjamin, PhD, an investigator in BIDMC's Department of Pathology and Associate Professor of Pathology at Harvard Medical School.

"First, unlike healthy blood vessels which are uniform in structure, a tumor's blood vessels balloon and narrow, forming a highly irregular shape. Second, the layer of smooth muscle that you would expect to find covering the blood vessels is inadequate, often resulting in only intermittent coverage. And last, a tumor's blood vessels are overly permeable or leaky."

The hypothesis that blood vessel formation in tumors is essential for the growth and spread of cancer was first proposed in the early 1970's, and in 1983, it was shown that tumors secrete a factor called VEGF (vascular endothelial growth factor) that induces the permeability associated with blood vessels in cancer.

In this new study, Benjamin and first author Thuy Phung, MD, PhD, of BIDMC's Department of Pathology, hypothesized that the Akt pathway was mediating many of the functions of VEGF in tumors, including the stimulation of blood vessels with abnormal struct
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
14-Aug-2006


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