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Scientists stalk PPAR-gamma, find novel cancer connection

In laboratory tests on multiple myeloma cells, University of Rochester researchers found that this type of cancer expresses a protein that makes it an easy target for an existing class of diabetes drugs. After more investigation, they hope the discovery will lead to a new, targeted therapy for myeloma patients.

"To our knowledge, this is the first time anyone has shown that multiple myeloma cells are sensitive to these agents, and we found multiple myeloma cells are killed quite effectively," says lead author Richard P. Phipps, Ph.D., professor of Environmental Medicine and of Oncology at the University of Rochester Medical Center.

The research was reported in the November issue of Clinical Immunology.

The drugs in question are from the thiazolidinedione (TZD) class of anti-diabetic therapies, known as PPAR-gamma ligands. They bind to PPAR-gamma, a protein associated with multiple myeloma and many other cancers, as well as chronic inflammation and diabetes. When the drugs bind to PPAR-gamma, at least in laboratory experiments, the cancerous cells are destroyed.

PPAR-ligands are emerging as a new type of cancer therapy because they directly target errant cells and stop tumor growth, at least in animal models. Phipps' laboratory also found that the PPAR-ligands currently used in anti-diabetic drugs could induce a type of cell death called apoptosis. This is significant because multiple myeloma is very difficult to treat, as it is usually resistant to drug-induced apoptosis.

Another encouraging factor is that the anti-diabetes drugs were able to kill the multiple myeloma cells, despite the fact that myeloma produces its own growth factor (Interleukin 6), which usually enables the cancer to multiply more effectively. Furthermore, the Phipps lab found that the effectiveness of the TZD drugs was enhanced when combined with Vitamin A-like compounds.

Co-investigator Steven Bernstein, M.D., who treat
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Contact: Leslie Orr
leslie_orr@urmc.rochester.edu
585-275-5774
University of Rochester Medical Center
8-Dec-2004


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