Protein linked to chemo-drug resistance

SAN DIEGO, Aug. 28 (UPI) -- U.S. researchers say they have linked a genetic variant of a protein to resistance to the chemotherapy drug cisplatin.

The University of California, San Diego, researchers found that when a specific variant form of PMS2 -- a cell repair protein that fixes DNA mistakes and plays a role in cell death -- is active, cisplatin doesn't kill cancer cells the way it normally does.

In experiments using mouse cells, the researchers, led by Jean Wang and Richard Kolodner, found PMS2 normally sensitized cells to cisplatin, causing cell suicide. However, one variant -- R20Q -- failed to activate another protein called p73 which usually begins the cascade of steps leading to cell suicide in the cancer cells.

The findings, reported online in the journal Proceedings of the National Academy of Sciences, are important to understanding how personalized therapies may be developed for patients, the researchers said.

"We don't know how many people have this PMS2 variant," Yang said, noting that cisplatin is the first-line therapy for testicular and ovarian cancers. "We would like to take these findings to human tumor samples. If we could find out which individuals carry this variant, it might change our decisions about treating them with cisplatin."