PARP Inhibitor Combination Therapy Could Enhance Cancer Treatment

Tumors that over-express a specific oncogene may benefit from combination therapy regardless of cancer type.

A recent study found that combining PARP inhibitors with other targeted inhibitors may enhance breast cancer treatment.

C-Met is an oncogene overexpressed in many different types of cancers. Researchers found that by combining PARP inhibitors, which are still mostly in clinical trials for breast cancer, with inhibitors that targeted c-Met, it could enhance current treatment results.

Investigators found that c-MET is introduced into PARP1, which increases enzymatic activity. When this occurs, it makes cancer cells resistant to PARP inhibition and blocks c-MET’s interaction with PARP.

"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," said lead study investigator Mien-Chie Hung, Phd.

The study, published Nature Medicine, was conducted at The University of Texas MD Anderson Cancer Center.

"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," Hung said.

Recently, the FDA approved olaparib, a PARP inhibitor used to treat ovarian cancer with BRCA --- a mutant breast cancer gene. However, the inhibitors are still going through clinical trial phases for breast cancer.

"BRCA1 and BRCA2 play essential roles in repairing DNA double strand breaks and a deficiency of BRCA proteins sensitizes cancer cells to PARP inhibition," Hung said. "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."