New Findings May Enhance PARP Inhibitor Therapy in Breast Cancer
Findings from a new study reveal that the activity of PARP inhibitors, an emerging class of drugs being studied in cancer clinical trials, may be enhanced by combining them with inhibitors targeting the oncogene c-MET, which is overexpressed in many cancers. The findings resulting from in vitro and mouse model studies were published by Du et al in Nature Medicine.
Study lead investigator Mien-Chie Hung, PhD, Chair of Molecular and Cellular Oncology at The University of Texas MD Anderson Cancer Center, believes the study results may hold promise for future treatment of breast cancer and possibly other cancers.
“These findings may predict tumor resistance to PARP inhibitors, and suggest that treatment with a combination of c-MET and PARP inhibitors may benefit patients bearing tumors with high c-MET expression who do not respond to PARP inhibition alone,” said Dr. Hung.
Study Findings
While PARP inhibitors are still in the clinical trial phases for breast cancer, the U.S. Food and Drug Administration recently approved the PARP inhibitor olaparib (Lynparza) for treatment of women with ovarian cancer and BRCA mutations.
“BRCA1 and BRCA2 play essential roles in repairing DNA double-strand breaks, and a deficiency of BRCA proteins sensitizes cancer cells to PARP inhibition,” said Dr. Hung. “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.”
Dr. Hung's team discovered that c-MET associates with and phosphorylates PARP1, which increases its enzymatic activity. This process essentially renders cancer cells resistant to PARP inhibition. By blocking c-MET's cancer-friendly interaction with PARP, cancer cells lose this resistance to the therapy.
“Our study findings raise the interesting possibility that cancer patients with tumors that overexpress c-MET may benefit from this combination therapy, regardless of cancer type,” concluded Dr. Hung.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
