Cancer treatment: ‘Exciting’ new drug targets tumours created by faulty BRCA genes

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The Institute of Cancer Research (ICR) and Cancer Research UK collaborated to create this potential new treatment for breast, ovarian, pancreatic and prostate cancers with the BCRA mutations. The NHS explained the faulty BRCA gene “affects around one in 400 people”. Women with the faulty BRCA1 gene, for example, have a 60 to 90 percent lifetime risk of breast cancer, and a 40 to 60 percent risk of ovarian cancer.

Crucially, research suggests that the POLQ inhibitors can kill cancer cells that have become resistant to PARP inhibitors – an existing cancer treatment.

Professor Paul Workman said “it’s exciting that the new POLQ inhibitors should provide a different approach to treating cancers with BRCA gene defects”.

The chief executive of ICR continued: “Most exciting of all is the potential of combining POLQ and PARP inhibitor drugs to prevent the evolution of BRCA-mutant cancers into more aggressive, drug-resistant forms – a major challenge that we see in the clinic.”

Study co-leader, Dr Graeme Smith, added: “These exciting pre-clinical results provide a clear rationale for future clinical studies with a POLQ inhibitor.”

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Clinical trials – to be conducted by Artios Pharma – are set to go ahead this year to determine the success of the drug.

A limited number of cancer patients will take the innovative new treatment in the next two years, with the hope that the drug will enter generalised cancer treatment plans by 2026.

The rationale behind the cancer drug

Scientists have known for quite some time that genetically removing the protein POLQ kills cancer cells with BRCA gene defects.

BCRA genes and POLQ are involved in repairing DNA, and cancer cells can survive without one of them.

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However, if both the BRCA genes and POLQ protein are “switched off”, cancer cells can no longer repair their DNA and they die.

“By killing cancer cells with BRCA gene mutations, while leaving normal cells unharmed, POLQ inhibitors could offer a treatment for cancer with relatively few side effects,” said the ICR.

Professor Chris Lord elaborated: “All cells have to be able to repair damage to their DNA to stay healthy – otherwise mutations build up and eventually kill them.

“We have identified a new class of precision medicine that strips cancers of their ability to repair their DNA.”

Professor Lord is “very keen” to see how the POLQ inhibitors perform in clinical trials.

Chief executive at Cancer Research UK, Michelle Mitchell commented on the new drug treatment.

“More than 25 years ago we helped discover the BRCA gene, which spurred on our scientists to work with others to develop PARP inhibitors,” she said.

“But we are always trying to find newer and better ways to outstep cancer, especially when it stops responding to current treatments.

“By revisiting weaknesses in the BRCA repair pathway, researchers have not only found a way to make PARP inhibitors more effective, but they may have also identified an entirely new class of targeted drugs for BRCA cancers.

“We look forward to seeing if these promising results in the lab transfer into benefits for patients when tested in trials.”

If you have a family history of cancer, you can speak to your doctor about having a predictive genetic test that determines if you have the faulty BRCA genes.

A positive test result does not guarantee you will develop cancer, it only highlights whether or not you’re at an increased risk.

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