Researchers from the The Institute of Cancer Research, London and Artios have identified a new class of drugs – POLQ inhibitors – which could have potential for patients with BRCA-mutated tumours.
Scientists have known ‘for some time’ that removing the POLQ protein killed cells with BRCA gene defects, although a POLQ inhibitor had yet to be identified.
In the new research, scientists identified prototype drugs that inhibit POLQ and also killed cancer cells with BRCA gene mutations.
The drugs, while specifically killing BRCA-mutated cancer cells, left healthy cells unharmed. The researchers also found that POLQ inhibitors work ‘very well’ alongside PARP inhibitors.
The researchers believe that administering a POLQ inhibitor in combination with a PARP inhibitor in patients with BRCA-mutated cancers may prevent resistance from emerging.
The study, funded by Artios, Cancer Research UK and Breast Cancer Now, was published yesterday in Nature Communications.
Following the promising results, researchers are planning to evaluate the new drug class in upcoming clinical trials, led by Artios.
“It’s exciting that the new POLQ inhibitors should provide a different approach to treating cancers with BRCA gene defects – and particularly that this class of drugs should retain their activity in cancers that have developed resistance to PARP inhibitors,” said Paul Workman, chief executive of The Institute of Cancer Research, London.
“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,” he added.
“Drug resistance is a major hurdle that we must tackle to stop women dying from breast cancer, so it is also exciting that POLQ inhibitors offer a hope of overcoming resistance in some cases,” said Simon Vincent, director of research, support and influencing at Breast Cancer Now.
“We hope that future research will confirm that POLQ inhibitors can benefit people with breast cancer in these ways,” he added.