The Institute of Cancer Research has discovered a genetic mutation in samples of some men's tumours that could make them particularly susceptible to immunotherapy treatment. The researchers are now committed to running clinical trials to prove if their theory is right.

4 Sep 2018

A new investigation of tumour samples by the Institute of Cancer Research (ICR) suggests some men with advanced prostate cancer that carries a certain genetic fault may respond unusually well to immunotherapy. The results are a boon for these men, as their type of cancer is more likely to become treatment-resistant and kill quicker than other advanced disease.

Immunotherapy is a type of treatment that uses the body’s own immune system to help fight disease. It has already been proven to be effective in many other types of cancer, and now this ICR study adds to increasing evidence that it could also be effective for small numbers of men with advanced prostate cancer.

Professor Johann de Bono

"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," says Professor Johann de Bono (pictured above), Regius Professor of Cancer Research at the ICR, who headed up the research.

The researchers discovered that men with these 'mismatch' repair mutations only live about half as long as others whose advanced prostate cancer don’t carry such mutations, after examining 127 tumour biopsies and genetic data from a further 254 patients.

"We discovered that [these] tumours have key hallmarks which make them particularly likely to respond to checkpoint inhibitor immunotherapy," says Professor de Bono. "We are now developing tests that could pick out patients with these mutations, and we’re running new clinical trials to see if immunotherapy can offer new hope for these men."

Detection of protein key to targeting treatment

Published in the Journal of Clinical Investigation today, the study looked at the levels of a protein called PD-L1 on the surface of cancer cells as a way of indicating the likely response to checkpoint inhibitor immunotherapy. Targeting PDL-1 activity with an immune checkpoint inhibitor takes the 'brakes' off the immune system, setting it free to attack cancer cells.

The researchers found that half of tumours with mismatch repair mutations had high levels of PD-L1, compared with only 9.8 per cent without these mutations – making men with these tumours much more likely to benefit from a checkpoint inhibitor drug.

They also found that over half of tumours with mismatch repair mutations had been invaded by T cells from the patient’s immune system – another indicator that immunotherapy may well be effective.

What we think about the new research

"This research brings together two of the most important emerging areas in prostate cancer research: immunotherapy and precision medicine," says Dr Matthew Hobbs, our Director of Research.

"This important study has identified a group of men with aggressive prostate cancer who are most likely to benefit from this treatment approach. Although it’s still early days, the results provide another piece of the jigsaw which will eventually help doctors decide on the best treatment for each individual man.

"The Movember Foundation and Prostate Cancer UK are currently funding more research in this area to build on these results and ensure the right treatments are given to the right man as soon as possible."

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