The popular pain drug Celebrex activates a "death receptor" that makes cancer cells self-destruct, a new study shows.

Normal doses of Celebrex (search) may be too low to trigger significant anticancer effects. But the new finding points the way to new Celebrex-based anti-cancer therapies. It also suggests that combining Celebrex with new kinds of designer molecules might have powerful anti-cancer effects.

The findings come from Xiangguo Liu, PhD, Shi-Yong Sun, PhD, and colleagues at Winship Cancer Institute at Emory University School of Medicine in Atlanta. The study appears in the Dec. 1 issue of the Journal of the National Cancer Institute.

"The approach of [Celebrex]-based combination regimens for cancer chemoprevention and therapy and identification of [Celebrex]-derived novel anticancer drugs with more potent efficacy should be explored further," Liu and colleagues write. "We suggest that death-receptor induction be evaluated as a target for screening novel [Celebrex]-based anticancer drugs."

Indeed, the researchers note that new Celebrex-based compounds with more powerful anticancer activity have already been discovered.

The researchers' studies confirm earlier work showing that Celebrex fights cancer in a completely different way than it fights pain. They found that the drug plugs into a molecular keyhole on the outside of cancer cells – the so-called death receptor. This turns on a self-destruct program.

A helper molecule called TRAIL greatly increases this anticancer effect. Liu and colleagues suggest that a drug based on this molecule might be given together with Celebrex.

The FDA has already approved Celebrex for the treatment of adenomatous polyposis, an inherited disease that predisposes a person to colon cancer. Clinical trials are exploring whether Celebrex – alone or in combination with other agents — can prevent or fight several different kinds of cancer, including lung cancer.

By Daniel J. DeNoon, reviewed by Brunilda Nazario, MD

SOURCES: Liu, X. Journal of the National Cancer Institute, Dec. 1, 2004; vol 96: pp 1769-1780.