New Imaging Test Targets Enzymes for Ovarian Cancer Treatment
Researchers from the Perelman School of Medicine at the University of Pennsylvania have discovered a way to better identify candidates for an emerging ovarian cancer treatment. A new imaging test helps the researchers determine patient enzyme levels, a key factor in candidacy for the treatment.
The treatment blocks the enzyme Poly (ADP-ribose) Polymerase 1 (PARP-1), which helps damaged cancer cells repair their DNA and survive. Currently, epithelial ovarian cancer patients with BRCA1 mutations are considered candidates for PARP inhibitor treatment; thanks to the imaging, patients without the BRCA mutation also can be considered.
“Research exists that shows PARP inhibitors can be effective in the treatment of BRCA1 mutated cancer, but there are no good existing methods to explore how mutations within BRCA genes effect PARP-1 expression,” said the study’s lead author Mehran Makvandi, instructor of radiology. “We wanted to validate our radiotracer technology as a quantitative biomarker for PARP-1 with the goal of selecting patients who could benefit from PARP inhibitor therapy.”
The researchers used genetic editing to compare the effects on cancer cells of losing PARP-1 against the effects of gaining BRCA1.
“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,” said Dr. Makvandi. “Furthermore, sensitivity to PARP inhibitors was reflected in the measures of PARP-1 expression provided by our new radiotracer method.”
The researchers then used clinical PET scans to measure PARP-1 in a series of patients with epithelial ovarian cancer, becoming the first team to do so. They used FluorThanatrace (FTT), a PET imaging agent developed by the study’s co-author Robert Mach, the Britton Chance Professor of Radiology at Penn. FTT allows for non-invasive clinical assessment of PARP-1.
In addition, “We can quantify PARP-1 at baseline, and then use serial imaging studies to directly measure the effects of PARP inhibitors,” Dr. Makvandi said.