Scientists have identified a new class of drugs that could lead to potential treatments for cancers which are caused by mutations in the BRCA gene.
These drugs, known as POLQ inhibitors, are able to destroy cancer cells with BRCA mutations without damaging healthy cells.
The study, published in Nature Communications, offers new hope for cancers caused by defects in the BRCA gene, such as breast, ovarian and prostate cancer, which have become resistant to existing treatment involving another class of drugs known as PARP inhibitors.
Study co-leader Chris Lord, professor of cancer genomics at the Institute of Cancer Research (ICR), London, said: “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.
“This new type of treatment has the potential to be effective against cancers which already have weaknesses in their ability to repair their DNA, through defects in their BRCA genes.
“And excitingly, the new drugs also seem to work against cancer cells that have stopped responding to an existing treatment called PARP inhibitors – potentially opening up a new way of overcoming drug resistance.”
A BRCA mutation occurs when the DNA that makes up the gene becomes damaged.
When a BRCA gene is mutated, it may no longer be effective at helping prevent cancers such as breast, ovarian, pancreatic and prostate.
For their study, scientists at the ICR and pharmaceutical company Artios treated cancer cells grown in the lab with the faulty BRCA gene using POLQ inhibitors.
Tests were also conducted on rats, which showed that POLQ inhibitors were able to shrink cancers that had become resistant to PARP inhibitors.
They also found that cancer cells treated with POLQ inhibitors were stripped of their ability to repair their DNA and died, but normal cells did not.
The experts said this offers hope that POLQ inhibitors could be a potential treatment for cancer with relatively few side effects.
Based on their findings, the researchers are planning to run clinical trials as part of the next steps.
Study co-leader Dr Graeme Smith, chief scientific officer at Artios Pharma, Cambridge, said: “These exciting preclinical results provide a clear rationale for future clinical studies with a POLQ inhibitor.
“At Artios, we are on track to initiate our POLQ clinical programme before the year end to explore POLQ inhibition in the sensitive cancer types that this study has uncovered.”
Commenting on the findings, Dr Simon Vincent, director of research, support and influencing at Breast Cancer Now, said: “Men and women with a change in one of their BRCA genes are at greater risk of being diagnosed with breast cancer, and around 5% of the 55,000 cases of breast cancer diagnosed in the UK each year are caused by an inherited altered gene, which includes BRCA1 and BRCA2 genes.
“It’s therefore hugely exciting that POLQ inhibitors could provide a targeted treatment option for people whose cancer is caused by altered BRCA genes.”
