Scientists have identified a one sub-group of aggressive prostate cancer patients that may benefit particularly well from immunotherapy.
The study was carried out by an international team of scientists at The Institute of Cancer Research, London, UK, and the Dana-Farber Cancer Institute in the US.
They examined survival rates and tumour DNA among 124 men with advanced prostate cancer, and further genetic information from 254 other patients.
This suggested that men with specific genetic faults called mismatch repair mutations in their tumours have much lower survival – an average of 3.8 years after initiating treatment, versus 7.0 years.
These faults raise the rate of DNA errors because they cannot effectively correct single-letter mistakes in their DNA code. As more mutations are acquired, the tumour can develop drug resistance.
The team also found that these unstable tumours are more likely that other forms to stimulate an immune response, meaning that they should be particularly susceptible to immunotherapy.
Details were published yesterday evening (4 September) in The Journal of Clinical Investigation.
They state that clinical trials are already starting to test so-called checkpoint inhibitor immunotherapy in this group of patients. This treatment "takes the brakes off the immune system", say the scientists, enabling it to attack cancer cells.
Lead researcher, Professor Johann de Bono, said: "Our study found that some men with advanced prostate cancers have genomic mutations in their tumours that make the disease unstable, aggressive and resistant to standard therapies.
"We discovered that tumours with mismatch repair mutations have key hallmarks which make them particularly likely to respond to checkpoint inhibitor immunotherapy. We are now developing tests that could pick out patients with these mutations."
de Bono, J. et al. The Journal of Clinical Investigation 4 September 2018
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