UCLA CELL-RESISTANCE STUDY COULD AID CANCER FIGHT.

Byline: Sherry Joe Crosby Daily News Staff Writer

Two UCLA researchers say they have discovered why some cancer cells reject a wide spectrum of drugs used in chemotherapy, providing another line of attack on one of the leading causes of deaths among Americans.

Leonard H. Rome, senior associate dean for research at the UCLA School of Medicine, and Valerie A. Kickhoefer, a research biochemist at the Westwood campus, say their findings could help oncologists defeat drug-resistant cells - one of the biggest obstacles in the treatment of the sometimes fatal disease.

``That's exciting,'' said Rome, the principal investigator and a member of the Jonsson Comprehensive Cancer Center at the University of California, Los Angeles. ``It could really lead to something new - drugs that will be effective in this very important problem of multiple-drug resistance.''

The pair's discovery will be published today in The Journal of Biological Chemistry.

Dawn Willis, a molecular biologist and scientific program director for the American Cancer Society, said while the discovery could mean dramatic new drug therapies it will be years before the public derives any benefit from the findings.

``It may help in drug design in the future. I don't see any immediate application,'' Willis said.

The four-page article describes the correlation between drug-resistant cells and the number of vaults, large barrel-shaped protein particles that transport cell components from one part of a cell to another.

Drug-resistant cells are able to pump out chemotherapeutic drugs before the drugs have time to take effect. The researchers said vaults are one of the pumps that cancer cells use to eliminate cancer-fighting drugs.

The more vaults in a cell, the more likely the cell is to reject wide varieties of anti-cancer drugs, a condition known as multidrug resistance, the researchers said.

``That finding opens new avenues for designing ways to increase the sensitivity to drugs of cells that have become multidrug resistant,'' said Kickhoefer, a Sherman Oaks resident.

Multidrug resistance is the one of the biggest problems in treating cancers, Rome said.

``When you start to treat cancers, in a very large number of cases, cells begin to resist drugs and that problem is compounded because once they learn to resist the poison, they also learn to resist a whole wide variety of chemotherapies,'' said Rome, a 19-year Tarzana resident.

The pair based their research on findings by Dutch scientist Rik J. Scheper, who in 1995 reported that specific multidrug resistant cells have unusually large amounts of a protein that comprise the main component of vaults.

Scheper showed that a high concentration of that protein in an otherwise healthy cell is the best indicator that the cell will eventually become resistant to cancer-fighting drugs.