Combining PARP Inhibitors With Other Inhibitor Effective in Ovarian Cancer

Recent research out of in Cell Reports found that combination of PARP inhibitors with another small molecule inhibitor may broaden the therapy’s ability to treat ovarian cancer.

“By blocking another member of the DNA repair pathway, PARP inhibitors are an effective strategy to kill BRCA-mutant cancer cells and have recently been approved for the treatment of ovarian cancer, but how to expand their utilities into BRCA-proficient cancers remained to be explored,” Rugang Zhang, PhD, deputy director of The Wistar Institute Cancer Center and professor and co-program leader of the Gene Expression and Regulation Program, said in a press release. “We identified an effective strategy to sensitize BRCA-proficient ovarian cancers to PARP inhibitors and extend their clinical efficacy to a larger group of patients.”

The researchers used a small molecule inhibitor to block the activity of the BRD4 transcriptional regulator, and combine that effect with a PARP inhibitor. Study researchers found that this strategy could significantly reduce tumor burden without increasing toxicity. However, this treatment strategy did not have an effect on tumor growth.

The researchers noted that their findings could impact the development of novel ovarian cancer therapies.

“The combined use of these inhibitors can be potentially applied to a broad spectrum of malignancies regardless of the BRCA genes mutational status,” Sergey Karakashev, PhD, co-first author of the study and a postdoctoral researcher in the Zhang Lab, said in the press release. “Therefore, we anticipate that our work will have far-reaching applications in the development of novel combinatory cancer therapeutics.”

—David Costill