Cancer cells, like other cells in the human body, rely for their growth on a rich supply of blood. They must be surrounded by an effective network of capillaries and larger blood vessels that nourish the cells. The medical term for the process of developing this network is angiogenesis.
In fact, fast-growing cancers are highly efficient at promoting angiogenesis. They produce angiogenesis promoters that create capillaries and a network of blood vessels around the tumor. The tumor is nourished with an increasing supply of oxygen-rich blood, and it grows and spreads (or metastasizes).
Understanding that angiogenesis is fundamental to the process of how tumors grow and metastasize, medical researchers started to investigate how they could slow down, stop, or reduce angiogenesis. If they could do this, they reckoned, they could starve the tumor to death - or at least slow its growth significantly. The National Cancer Institute has created an illustrated teaching tool to better understand how angiogenesis works.
A number of antiangiogenesis drugs, also called angiogenesis inhibitors or angiogenic inhibitors, have been developed. When administered to laboratory animals with tumors, they have caused the tumors to shrink or even disappear. Endostatin, combrestatin, angiostatin, thrombospondin, and vascular endothelial growth inhibitor (VEGI) are among these experimental drugs. See also: "Moving beyond chemotherapy: novel cytostatic agents for malignant mesothelioma," by H.L. Kindler in Lung Cancer August 2004; 45 Suppl. 1:S125-S127.
A few of these drugs are now being tested on humans. One of them, combrestatin, destroys the lining of blood vessels around tumors. Another, endostatin, acts by impeding the growth of new blood vessels around the tumors. For endostatin there have been some promising developments. Harvard's Dana-Farber Cancer Institute released an updated report on Phase 1 trials of the angiogenic inhibitor and says it exhibits virtually no toxicity even at high doses, while shrinking tumors in two of 28 advanced cancer patients and slowing disease progression in four others for more than six months.
This area of cancer research holds promise for the treatment of mesothelioma tumors, but it is very much in the early and experimental stages.
There are some anti-angiogenesis clinical trials and they can be located by searching the National Cancer Institute's clinical trials database. Most of the research is centered in Boston where the original angiogenesis research was performed by Dr. Judah Folkman's team at Children's Hospital. In early 2001, the NOVA program on PBS aired the story of Judah Folkman's scientific voyage in a program entitled "The Cancer Warrior" (aired 2/27/01). Link to a recent NOVA interview with Dr. Folkman or read FAQ about anti-angiogenesis. There has been criticism about Dr. Folkman's claims when scientists could not replicate the results that endostatin shrinks tumors by cutting off their blood supply.
Other medical centers where antiangiogenic tests are being performed include Brigham and Women's Hospital, Dana-Farber Cancer Institute and Massachusetts General Hospital in Boston, the University of Wisconsin Comprehensive Cancer Center, and the University of Texas M.D. Anderson Cancer Center in Houston.
Further Resources
- Angiogenesis Inhibitors in the Treatment of Cancer: An Interview with Lee S. Rosen, MD by Eric Sabo American Society of Clinical Oncology 39th Annual Meeting May 31, 2003 - June 3, 2003; Chicago, Illinois
- Anti-angiogenesis: The Challenges Ahead by Sara M. Mariani, MD, PhD Highlights From the 2003 Annual Meeting of the American Association for Cancer Research; April 5-9, 2003; Toronto, Ontario, Canada.
- Unfulfilled Promise of Endostatin in a Gene Therapy-Xenotransplant Model of Human Acute Lymphocytic Leukemia, Molecular Therapy, V5 (4): 352-359; April 2002, Wolfgang Eisterer, Xiaoyan Jiang, Thomas Bachelot, Robert Pawliuk, Carolina Abramovich, Philippe Leboulch, Donna Hogge and Connie Eaves (abstract found at www.sciencedirect.com)
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