Dr. Judah Folkman Reports Finding of Panel of Biomarkers in Platelets in Mice that May Permit Early Diagnosis of Cancer or Cancer Recurrence
March 27, 2006
Dr. Judah Folkman, the scientist whose discoveries founded the growing field of angiogenesis research, now reports the finding of a panel of biomarkers in platelets that may permit very early diagnosis of cancer. Working with mice bearing human tumors, Dr. Folkman and Dr. Giannoula Klement found that platelets took up angiogenesis regulatory proteins secreted by these tumors. When the microscopic tumors began to grow new blood vessels and grow, these angiogenesis regulatory proteins began to appear in the plasma as well as in the platelets. If this biomarker can be validated in patients, says Dr. Folkman, it may be used in conjunction with other biomarkers to diagnose the recurrence of cancer years before such a minute tumor burden became symptomatic or able to be located by conventional methods such as imaging.
Dr. Folkman described the work April 2 in the keynote lecture of the American Association of Anatomists meeting, part of Experimental Biology 2006 in San Francisco.
The finding of selective uptake of angiogenesis regulatory proteins secreted by tumors also marks a novel function of platelets, the blood cells responsible for blood coagulation and repair of damaged blood vessels.
The "platelet angiogenesis proteome" provides a stable, sensitive, and reliable biomarker for very early diagnosis of cancer, says Dr. Folkman. It could be used to detect recurrence of cancer or to diagnose a new primary tumor, for example in women with the mutated breast cancer gene who have not yet developed a clinically detectable cancer.
In the 1970s, Dr. Folkman proposed a then daring hypothesis that tumors could not grow or metastasize without angiogenesis: growing or recruiting blood vessels in order to have their own blood supply. During previous decades, Dr. Folkman's laboratory also discovered the first angiogenesis inhibitors and initiated clinical trials of antiangiogenesis therapy. Last year, the FDA approved the first angiogenesis inhibitor, Avastin, for patients with advanced color or rectal cancer.
Antiangiogenesis compounds do not attack the tumor, as chemotherapies do, but instead turn off the endothelial cells that are essential for new blood vessel growth. Without a blood supply, the tumor eventually stops growing -- with few if any adverse effects on the organisms. The body also is less likely to become resistant to antiangiogenesis drugs, a common problem with traditional chemotherapy.
In addition to the novel platelet biomarker described at the AAA lecture, the Folkman team also has developed other specific and sensitive angiogenesis-based biomarkers in blood and urine capable of detecting microscopic human cancers in mice. In pre-clinical studies, antiangiogenesis therapy of these mice causes the biomarkers to decline to normal levels.
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