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Discovery determines best PARP inhibitor candidates for ovarian cancer

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This is a CT scan of an ovarian cancer. Scientists in Australia have figured out which ovarian cancer patients are best suited for drugs called PARP inhibitors.

By Allen Cone, UPI

Scientists have figured out which ovarian cancer patients are best suited for drugs called PARP inhibitors.

Researchers in Australia determined which high-grade serious ovarian carcinoma patients should respond to the enzyme poly ADP ribose polymerase inhibitors. The findings were published Friday in the journal Nature Communications.

"For the past two decades, it was thought that ovarian cancer patients whose cancer's BRCA1 genes are 'silenced' -- or methylated -- had faulty DNA repair and therefore were good candidates for PARPi treatment," Dr. Clare Scott, a researcher at the Walter and Eliza Hall Institute, said in a press release. "Yet the puzzling thing was we were unable to predict the patients for which the drugs would work."

The researchers noted one-third of the patients with BRCA1 mutant genes failed to benefit from the treatment. And even when patients respond, the majority relapse within one year.

In their research, colleague Olga Kondrashova said they discovered subtle differences in some BRCA1 methylated cancers, which explained why only some patients would respond to the drug.

"It was suddenly clear that all patients in the group could not be treated the same way," Kondrashova said. "We discovered that some of the patients had what could be described as 'incomplete' BRCA1 methylation where not every gene copy was 'switched off.'"

They found out incomplete methylation isn't enough to cause faulty DNA repair in cancer cells and in turn why PARPi isn't going to be effective for some patients. But the researchers say patients with complete methylation in their cancer who were responsive to the treatment "should not be discounted."

They used sophisticated laboratory models called patient derived xenografts, or PDX.

"PDX models are powerful because they mimic the complexity of human tumors at key stages as the cancer progresses," Kondrashova said. "Like 'snap shots' in time, PDX models allow us to accurately track how each patient's cancer is changing or responding to treatment."

Tissue before and after treatment was donated by 12 patients from the Royal Women's Hospital, the Royal Melbourne Hospital and the Peter Mac.

"Like 'snap shots' in time, PDX models allow us to accurately track how each patient's cancer is changing or responding to treatment," Kondrashova said. "The success of this approach shows that a long-term, detailed analysis is invaluable for providing better patient care.

Scott said this development can lead to more personalized care.

"There is no 'one size fits all' approach for ovarian cancer care," Scott said. "We need to keep making these strides in understanding so we can better match patients with the right treatment for their cancer."

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Health - U.S. Daily News: Discovery determines best PARP inhibitor candidates for ovarian cancer
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