Phenanthridine Drug Cures Breast Cancer in Mouse Model

A class of drugs that inhibits the DNA-repair enzyme PARP-1 (polyADP-ribose polymerase-1) was found to effectively eliminate human breast tumors in a mouse xenograft model without damaging normal cells.

Investigators at Tel-Aviv University worked with MCF-7 and MDA231 breast cancer-cell lines growing under tissue culture conditions and after transplantation into immunocompromised nude mice. They treated the cancer cells in culture and the mice with a candidate drug, PJ-34, a potent phenanthridine-type compound known to be a PARP-1 inhibitor.

The investigators reported in the November 5, 2009 online edition of the journal Breast Cancer Research that PJ-34 treatment of nude mice with transplanted human breast cancer cells prevented tumor development. The mechanism that blocked tumor growth was identified as the arrest of the cancer cell cycle at the G2/M phase. Normal cells were able to overcome the inhibitory action of the drug after a temporary period of stasis, but the blockage in cancer cells was permanent. While the normal cells recovered with no apparent damage, the cancer cells died off and failed to develop into tumors.

Previous studies had shown that PARP-1 inhibitors were effective only on cancer cells with mutated BRCA genes, since pathways controlled by normal BRCA bypassed and compensated for those under the direction of PARP-1. However, in the current study breast cancer cells lacking the BRCA mutation were efficiently eradicated.

Senior author Dr. Malka Cohen-Armon, professor of physiology and pharmacology at Tel-Aviv University, said, "This research provides a new therapeutic approach for a selective eradication of abundant human cancers."

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