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Angiogenesis and Cancer - Page 2

© David Olle

Current clinical trials

Now that Dr. Folkman's theory is widely accepted, angiogenesis inhibitors are being studied in over 100 laboratories, including around 40 biotechnology companies. Clinical trials of around 20 experimental drugs are currently in progress. They range from Phase 1 to large scale Phase 3 trials that directly lead to FDA approval for marketing of the drugs. The drugs are designed to block angiogenesis at various stages, including blocking the activators, blocking matrix breakdown, or inhibiting the endothelial cells directly. 3 They are being tested against a broad range of cancers, including breast, lung, kidney, melanoma, brain and multiple myeloma. Of particular interest is the testing of thalidomide, which achieved notoriety in the 1960's, when it caused the birth of thousands of babies with limb abnormalities. It now appears the the fetal abnormalities were caused by thalidomide's action as a angiogenesis inhibitor.

Prospects

It is important to realize that the primary goal of angiogenesis inhibitors is to keep cancers in check, rather than to effect a complete cure. It would, therefore, most likely require lifetime treatment. Since angiogenesis inhibitors are directed toward normal epithelial cells, it is unlikely that drug resistance will be a problem, as is the case with chemotherapy drugs. Drug resistance develops because cancer cells are genetically unstable, and through mutations produce cells that are resistant to drugs.

Work is in progress to develop laboratory tests that could detect cancers based on the angiogenesis concept. The tests could have application in checking for secondary tumors after the surgeon has removed the primary tumors. 6

Finally, I should mention that many solid tumors have multiple defects in the expression of angiogenic regulators. These situations may rrequire treatment with several angiogenic inhibitors. 1

REFERENCES

1.Burstein, H. Molecular Targets for Novel Cancer Treatments: Tumor Vaccines and Angiogenesis. American Society of Clinical Oncology 36th Annual Meeting, Day 4-May 23, 2000. Medscape

2. Cancer Trials Angiogenesis Inhibitors in Cancer Research

3. Cancer Trials Angiogenesis Inhibitors in Clinical Trials

4. Gaiso, M. Antiangiogenesis: A New Anticancer Therapy? Medscape Oncology 2(1), 1999

5. Lush, R. et.al., Review of Three New Agents that Target Angiogenesis, Matrix Metalloproteinases, and Cyclin-Dependent Kinases Moffitt

6. Williams, R. Angiogenesis Research Making Steady Strides Urology Times March 2001

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