Penn scientists explain utility of PARP-1 in treating ovarian cancer
Researchers at the University of Pennsylvania School of Medicine have identified a novel biomarker—as well as a way to image that biomarker non-invasively—for PARP inhibitors in women with ovarian cancer.
Epithelial ovarian cancer is one of the deadliest types of cancer in women, with more than 70 percent of patients presenting to the hospital with already-advanced disease. PARP inhibitors, or targeted therapies that kill cancer cells while sparing non-mutated tissue, have emerged as potential solutions for improving quality of life in these women.
“PARP inhibitors are effective in a broad population of patients with ovarian cancer,” Penn radiology professor Mehran Makvandi, PharmD, and colleagues wrote in the Journal of Clinical Investigation. “However, resistance caused by low enzyme expression of the drug target PARP-1 remains to be clinically evaluated in this context.”
PARP-1 needs to be present for PARP itself to function, the authors said, and they hypothesized the biomarker was variable between ovarian cancer patients. To test its presence and efficacy, the researchers used CRISPR/Cas9 gene editing to delete PARP-1 from ovarian cancer cells, comparing PARP’s reaction to PARP-1’s absence with a control group retaining PARP-1.
According to the study, cancer cells without PARP-1 showed less DNA damage and less responsiveness to PARP than those with PARP-1. Decline in function ran deep in some cases, in once instance reaching a 1,000-fold decrease in sensitivity to the PARP inhibitor.
“These findings show that PARP-1 is required for PARP inhibitors to do their job,” Makvandi said in a Penn release. “These data also demonstrated the clinical need to evaluate PARP-1 levels in BRCA cancers to better understand which patients are likely to benefit and which may be resistant.”
A small-scale clinical trial comprising just 10 patients also found that FluorThanatrace, a tracer designed by Penn radiologist Robert H. Mach, PhD, for the project, was able to bind to PARP-1, allowing the biomarker visibility on PET scans. The higher the level of PARP-1 a tumor expressed, the more tracer bound to the tumor, the authors wrote.
“This is proof-of-concept that we not only have a potential biomarker for the effectiveness of PARP inhibitors, but we also have a non-invasive imaging technique to find that biomarker in ovarian cancer patients,” Makvandi said.
After graduating from Indiana University-Bloomington with a bachelor’s in journalism, Anicka joined TriMed’s Chicago team in 2017 covering cardiology. Close to her heart is long-form journalism, Pilot G-2 pens, dark chocolate and her dog Harper Lee.