Giving more women access to game-changing ovarian cancer drugs

Giving more women access to game-changing ovarian cancer drugs

Illuminate newsletter header, Spring 2021
September 2021

Professor Clare Scott
Professor Scott and colleagues showed ovarian cancers  
that silence a gene involved in DNA repair were susceptible
to PARP inhibitors. 

Australian women with ovarian cancer could benefit from game-changing cancer treatments called PARP inhibitors, thanks to WEHI researchers.

The study, led by WEHI researchers Dr Ksenija Nesic, Dr Matthew Wakefield and Professor Clare Scott, with collaborators at QIMR Berghofer and the University of Melbourne, and in the US, identified a new group of patients who were likely to benefit from the therapy and should be included in trials of PARP inhibitors. 

‘Silencing’ key to drug response 

Dr Nesic said the research team found ovarian cancers that were sensitive to PARP inhibitors had changes that silenced a gene, called RAD51C, which is involved in DNA repair. 

“We observed that ovarian cancers with epigenetic marks, which silenced or ‘switched off’ the RAD51C gene, were susceptible to PARP inhibitor therapy,” she said. 

“The silencing of RAD51C has to be complete for PARP inhibitors to work – if the cancer has any residual DNA repair capabilities, or if these epigenetic marks are lost during treatment, the cancer becomes resistant to the PARP inhibitor therapy. 

“This indicates that women should be closely monitored for changes that affect gene silencing, which could render their cancers resistant to therapy,” she said. 

Unprecedented success 

Professor Scott is joint head of clinical translation at WEHI and an oncologist at the Royal Melbourne Hospital, the Royal Women’s Hospital and the Peter MacCallum Cancer Centre. 

She said PARP inhibitors were currently approved in Australia for treating women with BRCA1/2 mutated cancers, with unprecedented success. 

“In these women, first cancer recurrence is delayed by 3.5 years and, in advanced disease, progression-free survival is extended,” she said. 

Professor Scott said PARP inhibitors needed to be more widely available to women who have genetic mutations that inactivate RAD51C

“We’ve never been in a position to say the word cure before, but I am confident we are curing some women with a BRCA1 or BRCA2 mutation who receive a PARP inhibitor as an initial treatment, following chemotherapy. Now we want to see if we can cure women who do not have a BRCA mutation but have other mutations that render their cancers susceptible to PARP inhibitors.” 

 

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Two female scientists in a laboratory

Research led by Institute scientists is helping to match ovarian cancer patients with the right treatment for their cancer.