Researchers are investigating compounds that block a protein involved in cancer-cell DNA repair.

PHILADELPHIA—Researchers say they may have identified a novel approach to treating renal cell carcinoma (RCC). It involves using compounds that block a cancer gene’s repair mechanism so that chemotherapy is more effective.

“Cancer cells are notorious in their ability to rapidly create copies of themselves,” said Robert H. Weiss, MD, professor of nephrology at the University of California at Davis and chief of nephrology at the Sacramento VA Medical Center in California. “While the latest medications slow down that process, they do not tend to be curative and they have many side effects. We wanted to find ways to help make chemotherapeutics as effective as possible at the lowest doses possible.”

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New medications work by destabilizing cancers at the DNA level, thus reducing their ability to replicate. Knowing that the p21 gene has an important role in restoring cancer-cell DNA and potentially circumventing the benefits of those treatments, Dr. Weiss sought to identify compounds that could disrupt this pathway.

After testing thousands of compounds, Dr. Weiss and his colleagues found 12 that bind to recombinant protein p21. Additional tests showed that three of those compounds decreased p21 expression, blocking the ability of kidney cancer cells to mend and making them more responsive to DNA-damaging treatments.

Dr. Weiss and his team are now determining the lowest possible concentration at which the three candidates remain effective. The researchers’ findings appear in the January 2009 issue of Cancer Biology and Therapy.

“The results are very exciting, especially given how difficult kidney cancer has been to treat so far,” Dr. Weiss told Renal & Urology News. “Our work offers hope that in the future, these p21 inhibitors can be refined and used in concert with other conventional as well as novel cancer treatments to increase the comfort and life spans of patients with kidney cancer.”

He presented findings here at the American Society of Nephrology’s Renal Week conference.