PARP inhibitors for breast cancer are still in the testing phase, but the PARP inhibitor olaparib was recently approved by the U.S. Food and Drug Administration for the treatment of ovarian cancer with mutations in the BRCA breast cancer genes. BRCA genes may, despite their name, contribute to other cancer forms.
“BRCA1 and BRCA2 play essential roles in repairing DNA double-strand breaks and a deficiency of BRCA proteins sensitizes cancer cells to PARP inhibition,” lead investigator Mien-Chie Hung, from the University of Texas MD Anderson Cancer Center, said in a press release. “Combining c-MET and PARP1 inhibitors synergized to suppress growth of breast cancer cells. Similar synergistic effects were also observed in a lung cancer mouse model.”
In both cultured breast cancer cells and mouse models, the research team discovered that c-MET associates with and phosphorylates PARP1. The process increases PARP enzyme activity and essentially makes c