PARP inhibitors could be combined effectively with immunotherapies to destroy tumours in several kinds of cancer, according to a joint Anglo-French project.
The inhibitors were developed to work by damaging the DNA in tumours – but the latest studies show they also stimulate the immune system to attack tumours.
This is because they "unmask" the cancers by triggering the release of a range of molecules that alert the immune system to disease, according to the new findings.
The findings have been published in the Journal of Clinical Investigation and result from joint work between The Institute of Cancer Research, London, and the Institut Gustave Roussy, France.
Researchers studied lung tumours and cells from triple-negative breast cancers.
Clinical trials are now planned in patients with lung, breast, prostate and bladder cancer.
Researcher Professor Chris Lord said: “The findings of this study substantially change our understanding of how PARP inhibitors work. We now know that they not only kill tumours by damaging their DNA, but also by attracting immune cells to attack them – acting as a sort of double-pronged attack.
“Immunotherapy is a genuinely brilliant cancer treatment but generally only for the 10 to 20% of people who respond to it. Finding the tumour is half of the battle in immunotherapy so by attracting the immune cells to the tumour, PARP inhibitors could enable the immunotherapy drug to target their attack.”
Dr Kotryna Temcinaite, Research Communications Manager at Breast Cancer Now, said: “These are really promising findings that show once more just how important PARP inhibitors could be in treating a number of cancers. Not only do these drugs interfere with tumour cells’ ability to repair DNA but this study suggests they may have additional effects in initiating an immune response, which could then be exploited using other treatments.
“Activating the immune system to attack tumours is an exciting approach that is beginning to show promise in breast cancer. We now look forward to seeing how the combination of PARP inhibitors and checkpoint inhibitors may work in clinical trials for breast cancer patients.”
Journal of Clinical Investigation 9 March 2019
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