New research shows that blocking poly (ADP-ribose) polymerase-1 (PARP-1) may have a greater impact than restoring BRCA1 for the treatment of ovarian cancer, according to research presented at the 2017 American Association for Cancer Research Annual Meeting (April 1-5, 2017; Washington, DC; abstract 3716).
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Patients with epithelial ovarian cancer with BRCA1 mutations are considered candidates for treatments that target PARP-1 enzymes. By using PARP inhibitors, clinicians are able to trap the enzyme on cancer DNA, causing the cancer cells to die. However, there is no established method for measuring the enzyme levels of patients and offering subsequent treatment advice in regards to PARP inhibitors.
Researchers from the Perelman School of Medicine (Philadelphia, PA) attempted to alleviate this problem by using two different kinds of ovarian cancer cells: those with the BRCA1 mutation and those without the mutation. Researchers removed PARP-1 in BRCA1-mutant cancer cells and then exposed the cells to PARP inhibitors and the chemotherapy drug cisplatin. This process was repeated with the two kinds of cancer cells, but researchers left PARP-1 in the cells and compared results.
“We were able to compare the effects of losing PARP-1 to the effects of gaining BRCA1,” said Mehran Makvandi, PharmaD, RPh, ANP, lead author and instructor of Radiology at the University, in a press release (April 3, 2017). “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. Furthermore, sensitivity to PARP inhibitors was reflected in the measures of PARP-1 expression provided by our new radiotracer method.”
Additionally, researchers were able to use a new PET imaging agent—called FluorThanatrace—to measure PARP-1 in patients with epithelial ovarian cancer.
“PARP-1 expression has had only limited evaluation as a predictive biomarker for PARP inhibitor therapy, in part due to the lack of good tools for measuring levels in patients. We now have a technology that will allow us to clinically assess PARP-1 in a non-invasive way,” Dr Makvandi said.
FluorThanatrace is also able to observe PARP inhibitors in action to assess their effectiveness. Researchers note that they are now able to quantify PARP-1 at baseline and then use imaging to measure the effectiveness of the PARP inhibitors in action.—Zachary Bessette
