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Biomarkers of response to VEGF pathway-targeted therapy discovered for renal cell carcinoma

CHICAGO -- Angiogenesis inhibitors can be far more effective in treating metastatic clear cell renal cell cancer (RCC) - an aggressive form of the most common kind of kidney cancer that is also rich in blood supply - than traditional treatments, according to accumulating evidence. They can prolong life in about a third of patients, but researchers have not been able to identify the responding patients, prior to treatment.

Now, a research team from the University of California, San Francisco (UCSF) and the Cleveland Clinic, has found that patients whose tumors produce greater amounts of vascular endothelial growth factor (VEGF) and its receptor benefit most from these targeted treatments, because these proteins are the "targets" they are designed to go after.

"The more VEGF and VEGF receptor a patient's tumor has, the better these treatments seem to work," said the study's lead author, Erich B. Jaeger, Ph.D., a postdoctoral researcher at the UCSF Comprehensive Cancer Center. "This is very exciting because, if validated, a fairly simple test could help oncologists direct these new treatments to patients who can benefit most from them."

Results were presented at the first meeting on Molecular Diagnostics in Cancer Therapeutic Development, organized by the American Association for Cancer Research.

Clear cells RCCs often accumulate VEGF and other angiogenesis-related proteins due to mutation in the Von Hippel-Lindau (VHL) tumor suppressor gene. This gene was identified as the cause of the rare and inherited Von Hippel-Lindau disease, which is characterized by frequent development of clear cell renal tumors.

About half of non-inherited clear cell renal cell cancer is believed to result from mutations in the VHL gene, Jaeger said. The mutations prevent proper degradation of specific VHL target proteins, which leads to over-expression of VEGF and other proteins associated with angiogenesis, he said. These proteins cause the t
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Contact: Warren Froelich
froelich@aacr.org
215-440-9300
American Association for Cancer Research
13-Sep-2006


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