Details of promising cancer therapy shows for the first time

Visualization of action could lead to development of more potent, less toxic drugs

Scientists at Schering-Plough Research Institute are reporting what they say is the first atomic view that shows how a promising new class of cancer-fighting drugs works. The discovery may point the way to faster, better refinement of the drugs, according to the researchers. Several pharmaceutical companies are in a race to develop so-called farnesyl protein transferase (FPT) inhibitors, which incapacitate an enzyme recently found to activate many types of cancer. The drug detailed in this study is currently in clinical trials.

The findings will appear in the Journal of Medicinal Chemistry, which is published by the American Chemical Society (ACS), the world's largest scientific society. The peer-reviewed paper will be available on the ACS Web June 2 and is tentatively scheduled to appear in the journal's July 1 print edition.

FPT puts the finishing touches on a protein made under the direction of a mutated gene called ras (short for "rat sarcoma" because the gene's cancer connection was originally discovered in rats). Normally, a completed Ras protein attaches to cell membranes where it signals cells to grow, when appropriate. The mutation, which causes a single kink in the Ras protein structure, leaves it stuck in the "on" position. Out of control growth then ensues, causing cancer.

Since the gene's discovery in the early 1990s, the ras mutation has been linked to 90 percent of pancreatic cancers, 50 percent of colon cancers, and 30 percent of lung cancers. Researchers hope that by attacking FPT, instead of cell replication machinery directly, they can more specifically inhibit cancer and lessen collateral damage to normal cells.

A wave of FPT inhibitors has recently surged into clinical trials. They are one of the first types of mechanism-based anti-cancer agents targeted at a known protein molecule. While scientists had ideas about h

Contact: Charmayne Marsh
American Chemical Society

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