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Can resistance to PARP inhibitors be overcome in advanced ovarian cancers?

Wellbeing of Women, in partnership with Artios Pharma Limited, has invested £447,279 in Dr Patricia Roxburgh’s research to understand how, why and when some advanced ovarian cancers become resistant to a type of treatment called PARP inhibitors

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Around 7,500 people are diagnosed with ovarian cancer each year in the UK. In 2019, more than 1,350 women were told their tumour had spread to other parts of the body.

Tragically, ovarian cancer claims eleven lives every day in the UK.

Studies show that a type of treatment called PARP inhibitors, when used after chemotherapy, can help give women with advanced ovarian cancer more time with their loved ones. According to one study, the PARP inhibitor Olaparib was shown to delay disease relapse in advanced ovarian cancer patients by three years.

PARP inhibitors work by blocking a type of protein in our cells called poly-ADP ribose polymerase (PARP). Without access to this protein, cancer cells cannot repair themselves and die. Sadly, these drugs will eventually stop working for most patients as their tumours will become resistant to treatment.

The PARP Inhibitor Resistance Study (PAIRS), led by Dr Roxburgh, aims to find out how, why and when this treatment resistance occurs. We hope these findings will help doctors support and treat their patients more effectively and foster the development of new treatments able to sidestep this resistance.

Dr Roxburgh, Senior Clinical Lecturer and Honorary Consultant Medical Oncologist at the University of Glasgow, says: “PARP inhibitors have been shown to slow the progression of advanced ovarian cancer, but they’re not suitable for everyone. Some people may experience more severe side effects than others and for many, the treatment will stop working over time. We want to understand the reasons behind this and will be studying biomarkers in the blood to identify resistance at its earliest stage.

“This work will support the optimal prescribing of PARP inhibitors by clinicians and the development of strategies to prevent treatment resistance as well as new treatments for PARP inhibitor resistant disease.”

In a collaboration between the University of Glasgow and the University of Edinburgh, researchers will analyse samples of PARP inhibitor resistant tumours, collected as part of the PAIRS study.

Samples will involve tumour tissue taken from patients before PARP inhibitor treatment and again once the treatment is no longer effective. Dr Roxburgh and her team will examine molecular alterations to investigate what may have caused the treatment resistance.

Blood samples from patients will also be taken to see if markers of resistance can be detected in blood before disease progression is clinically detectable. This could allow doctors to adjust treatment more quickly in the future.