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Study sheds light on angiogenesis inhibitors, points to limitations, solutions
Date:3/2/2009

glioblastomas adapt to the angiogenesis-inhibiting drugs," Bergers says. "Scientists have reported results from a clinical trial in which a subset of patients developed tumor recurrence at many sites during the course of treatment with bevacizumab, an angiogenesis inhibitor. The recurrence was measured by MRI imaging."

"While anti-angiogenesis drugs are in general not proving to be an enduring success, this does not mean they aren't valuable therapies," she adds. "There is growing evidence that the drugs improve the quality of life, or even provide increased survival typically of a few months for glioblastoma patients. The drugs also can reduce edema in brain tumors and in some instances restore memory and speech."

A tumor's resistance to angiogenesis inhibitors differs from resistance to chemotherapy drugs, Bergers explains. The targets of anti-angiogenic therapy are normal cells that form the tubes of blood vessels, known as endothelial cells. Despite the fact that the drugs are still effective against these cells, resistance develops because the tumor finds additional pathways to circumvent the drug's inhibitory effect. One evasive tumor strategy involves tapping growth factors in the body other than VEGF for the new blood vessel growth they need. If the tumor can't rebuild its vasculature to a sufficient level, it can adopt another strategyto spread and become invasive.

In contrast, tumor cells resist chemotherapy by cell-intrinsic mechanisms such as mutating the gene targeted by the drug, or changing how the tumor takes up or expels the drug.

One class of anti-angiogenesis drugs works by blocking the action of an essential protein known as vascular endothelial growth factor, or VEGF, which normally stimulates new blood vessel growth. The strategy of starving tumors by depriving them of nutrients and oxygen in blood was first proposed in the early 1970s by the late Dr. Judah Folkman at Harvard Medical School. The idea took
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Contact: Jennifer O'Brien
jobrien@pubaff.ucsf.edu
415-476-2557
University of California - San Francisco
Source:Eurekalert  

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