University of Pennsylvania scientists have devised a new imaging test to measure the amount of PARP-1 enzyme in ovarian cancer patients, which could help identify which patients would benefit most from treatments that target PARP-1.
These treatments have the potential to vastly improve the outlook for patients with ovarian cancer. The American Cancer Society reports that only 20% of ovarian cancer cases are detected early. And the five-year survival rate for ovarian cancers that have spread is 73% for regional cases and just 29% for distant cases, versus 92% for localized ovarian cancer that's caught in the early stages.
PARP inhibitors, such as the recently approved rucaparib, make it difficult for ovarian tumor cells with the BRCA1 mutation to repair damaged DNA, which can lead to their death. While research has shown that PARP inhibitors can be effective in treating cancer patients with BRCA1 mutations, until now, there has been no good way to look at the interaction between the mutation and expression of PARP-1, said Penn's Mehran Makvandi, instructor of radiology and lead author on the new research, in a statement. The research was presented at the recent annual meeting of the American Association for Cancer Research.
Makvandi's team first studied two sets of ovarian cancer cells—those with a BRCA1 mutation and those without. They used gene editing to remove PARP-1 from some of the mutated cells. All of the cells were treated with a PARP blocker and the chemo drug cisplatin.
“We were able to compare the effects of losing PARP-1 to the effects of gaining BRCA1,” Makvandi said. “For a lot of the PARP inhibitors, losing PARP-1 led to as much or even more resistance to the treatment as the restoration of BRCA1 function." And the team was able to determine that their method could predict sensitivity to PARP inhibitors.
They then confirmed their results in patients using positron emission tomography (PET) imaging. With a new Penn-developed imaging agent, they measured PARP-1 in patients with epithelial ovarian cancer, the most common form of the disease.
Aside from identifying patients who might benefit from PARP-1 drugs, the new tracer and imaging method could be used to check whether the treatment is working, Makvandi said.