Combined Drugs Enhance Anticancer Activity

A novel approach to cancer chemotherapy combines two types of drugs, angiogenesis inhibitors to prevent formation of new blood vessels, and histone deacetylase (HDAC) inhibitors to allow DNA uncoiling and gene expression.

Both types of drugs have previously been found to have anticancer activity. In a study published in the September 15, 2004, issue of Cancer Research, investigators at Johns Hopkins University (Baltimore, MD, USA) combined the two drugs and studied the effect on cells growing in tissue culture and on tumors growing in mice.

They found that the anti-angiogenesis drug PTK787/ZK222584 reduced growth of prostate tumors in mice by 35% and of breast tumors by 54%. The histone deacetylase inhibitor NVP-LAQ824 reduced prostate cancer growth by 75% and breast cancer growth by 60%. When used together the two drugs reduced prostate cancer growth by 85% and breast cancer growth by 80%.

"Combining these two types of drugs may have a greater impact on cancer development than using them alone,” said senior author Dr. Roberto Pili, assistant professor of oncology at Johns Hopkins University. "Our idea is to attack the way cancers form new blood vessels by disrupting the angiogenesis process in two different cells. Such VEGF [vascular endothelial growth factor] inhibitors are known to have most effect on endothelial cells, the bricks and mortar of blood vessels. However, HDAC inhibitors target both endothelial and epithelial cells, which line organs, and are the origin of many cancers.”



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