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Immunotoxins: The Next Generation
New Cancer-Related Mutations Found in Breast & Colon Cancers
News from the AACR’s Molecular Diagnostics in Cancer Therapeutic Development Meeting
News from the AACR’s Frontiers in Cancer Prevention Research Meeting
Panitumumab approved for metastatic colorectal carcinoma
Bevacizumab use expanded to lung cancer
Histone deactylase inhibitor, vorinostat, now available
Trastuzumab expanded to adjuvant use in breast cancer
Imatinib: New uses approved, cardiac warning issued
Targeted mouse models useful in testing novel anticancer agents
Reviewed by Nicholas J. Vogelzang, MD
Although angiogenesis inhibitors may be more effective than traditional therapies in treating metastatic clear-cell renal cell cancer, it has not been possible to identify patients who might respond prior to treatment. Now, investigators from the University of California, San Francisco and the Cleveland Clinic have found that patients whose tumors produce larger amounts of vascular endothelial growth factor (VEGF) and its receptor derive the greatest benefit from these targeted treatments. Results were reported at the AACRÕs Molecular Diagnostics in Cancer Therapeutic Development Meeting, held in Chicago, Illinois, in September 2006.
When drug response was correlated to the level of VEGF and its receptor in the tumor samples, it was found that patients who had the highest levels of expression of VEGF receptor had the best response to therapy.
According to Erich B. Jaeger, PhD, a postdoctoral researcher at the UCSF Comprehensive Cancer Center, patients with clear-cell renal carcinoma often accumulate VEGF and other angiogenesis-related proteins due to mutation in the Von Hippel-Lindau (VHL) tumor suppressor gene. This gene causes Von Hippel-Lindau disease, which is characterized by frequent development of clear-cell renal tumors. About 50% of noninherited clear-cell renal cell cancers are thought to result from mutations in the VHL gene.
In the study, the investigators examined 43 tumor samples obtained before patients were scheduled to receive angiogenesis inhibitors and found that 25 contained VHL mutations. Of these, 15 had mutations that led to severe disruption of the normal structure of the VHL protein. When drug response was correlated to the level of VEGF and its receptor in the tumor samples, it was found that patients who had the highest levels of expression of VEGF receptor had the best response to therapy. These patients had nearly a doubling in time to progression, gaining about 6 months.
The research team is now preparing to conduct mutational analyses on a series of renal tumor samples taken from 700 patients who were treated with bevacizumab. Plans also call for improving the test by adding certain common mutations involving tumor suppressor genes and the ability to look for these mutations in paraffin-embedded tumors.
Bevacizumab is available as Avastin from Genentech, Inc.
Biomarkers of Response to VEGF–Targeted Therapy Found in Renal Cell Carcinoma
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