New Drugs Targeting Tumors Blood Vessels Demonstrate Potential
American Cancer Society
A new class of anticancer drugs, called vascular disrupting agents, or VDAs, may offer a valuable new tool to improve patient survival. A review of the research on this new drug class published May 10, 2004 in the online edition of CANCER, a peer-reviewed journal of the American Cancer Society, finds VDAs have been shown to lead to tumor reduction when used alone. In combination with conventional chemotherapy or radiation, studies show VDAs significantly improve outcomes. The full study will be available online via Wiley InterScience (http://www.interscience.wiley.com/cancer-newsroom), and will also appear in the June 15, 2004 print issue.
Unless they create their own blood vessels to tap into the body's nutritional supply, tumors cannot grow beyond 1-mm. But those vessels are morphologically and functionally abnormal, characterized by experts as "leaky." As a result, they cannot keep up with a tumor's exponentially expanding needs. But they still have clinical consequences, leading to an oxygen-deprived microenvironment which causes further genetic mutations of cancer cells that promote metastatic potential and cancers that are more resistant to treatment.
Tumor blood vessels have been a therapeutic target since first proposed by Dr. William H. Woglom of Columbia University in 1923. Studies have since shown that clamping off the blood supply to a tumor will cause tumor regression and cure. Current strategies include inhibiting blood vessel creation and preferential destruction of existing tumor supporting blood vessels.
VDAs target the established but immature blood vessels created by the tumor by either selectively attacking tumor vessel endothelium or exploiting other differences between normal and tumor-related blood vessels.
Led by Dr. Dietmar W. Siemann of the University of Florida's Shands Cancer Center in Gainesville, researchers reviewed the literature from existing studies to summarize the progress and efficacy of this class of drugs. The authors find that in preclinical trials, leading VDAs are able to disrupt existing blood vessels and reduce tumor blood flow. The impact on tumor tissue is direct induction of 80-90 percent necrosis and comparable secondary tumor cell death. However, VDAs leave a peripheral rim of viable tumor cells. When used in combination with chemotherapy, radiation therapy and hyperthermia in preclinical trials, VDAs enhance the efficacy of conventional anticancer treatments without adding to treatment toxicity.
Thus, "there is little doubt that the greatest potential utility of VDAs will lie in their combination with other therapies," conclude the authors.
Article: "Vascular-Targeting Therapies for Treatment of Malignant Disease," Dietmar W. Siemann, David J. Chaplin, Michael R. Horsman, CANCER; Published Online: May 10, 2004 (DOI: 10.1002/cncr.20299); Print Issue Date: June 15, 2004.
For more information, or to contact American Cancer Society, see their website at: www.cancer.org
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