A STING in the tail
What you need to know
- Some prostate cancers create a lot of inflammation in the body and are more likely to spread and recur after treatment.
- Professor Richard Bryant and Dr Eileen Parkes want to understand the role of the immune system in the cases with inflammation.
- If successful this could lead to clinical trials of treatments that can be combined with radiotherapy to reduce the recurrence of prostate cancer.
There is a large gap between advances being made in the immune treatment of other cancers compared to prostate cancer.
A combination of treatments alongside radiotherapy could help to prevent the immune system being hijacked by the cancer to help it grow and spread.
Hijacking the immune system
About 1 in 6 cases of prostate cancer have a lot of inflammation in the surrounding area. This is where the immune cells are activated and are on high alert to fight infections. Prof Bryant and Dr Parkes believe that this may be due to triggering a chain of events in the cell known as the STING pathway.
Previous work by Prof Bryant and his team found that prostate cancers which have activated the STING pathway have a lot of immune cells present. They believe that the STING pathway allows the cancer to hijack the immune system, so rather than working to destroy the cancer, the immune cells help it to grow more aggressively.
The effects of radiotherapy
Early evidence suggests that radiotherapy causes an immune response in prostate cancer. However, this immune response may make any surviving cancer cells more aggressive and likely to spread. Prof Bryant and Dr Parkes want to study how the STING pathway responds to radiotherapy. This will help them to find a way to stop the chain of events during radiotherapy and improve the treatment for patients.
To do this, they are studying prostate cancer in mice with different genetic changes. This includes mutations in the BRCA2 gene, which cause aggressive prostate cancer and may trigger the STING pathway. Radiotherapy causes damage to the DNA in cells, which triggers a response in the cell involving BRCA2. BRCA2 mutations in the cancer may cause it to respond differently to radiotherapy, so cancers with these mutations may benefit particularly from this approach.
Working towards a clinical trial
By understanding how the STING pathway is activated, the researchers hope to identify treatments that could get the immune cells working properly again. This research could also determine the best time to give this treatment in relation to the radiotherapy.
To confirm the study, the researchers would need to test the results in clinical trials. This could mean that men are given treatments alongside radiotherapy or shortly afterwards to prevent the remaining cancer cells hijacking the immune system.
From these findings, we aim to be in a position to design clinical trials in prostate cancer.
Grant information
Reference – MA-IMM19-003
Researcher - Prof Richard Bryant and Dr Eileen Parkes
Institution – University of Oxford
Award - £465,713