Immunotherapy could offer hope for some men with aggressive prostate cancers

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A group of men with especially aggressive prostate cancer may respond unusually well to immunotherapy, a major new study reports.

The research offers the possibility of effective treatment for men with prostate cancer who currently die from their disease much more rapidly than other patients – with clinical trials already starting.

An international team led by scientists at The Institute of Cancer Research, London, and the Dana-Farber Cancer Institute in the US showed why some men with advanced prostate cancer have much worse survival than others.

Their research found that men with prostate cancer who have specific faults in their tumours that make their DNA error-prone and unstable survive only half as long as other men with advanced disease.

And the findings have exciting implications for treatment – with the researchers showing that these unstable tumours are more likely to stimulate an immune response than other cancers. That should make patients with these aggressive prostate cancers particularly good candidates for immunotherapy.

The new study, published today (Tuesday) in the Journal of Clinical Investigation, looked at 127 tumour biopsies from 124 patients and genomic information from a further 254 patients acquired by the Prostate Cancer Foundation/Stand Up to Cancer International Prostate Cancer Dream Team.

The research was funded by the Prostate Cancer Foundation, Movember Foundation, Prostate Cancer UK, Stand Up to Cancer, V Foundation, the Stewart J. Rahr Foundation, Cancer Research UK, the Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre at The Royal Marsden NHS Foundation Trust and The Institute of Cancer Research (ICR).

The team found that 8.1 per cent of men with advanced prostate cancer had evidence of mismatch repair mutations in their tumours.

These men survived only 3.8 years after beginning prostate cancer treatment, compared with 7.0 years for men with advanced disease with no detectable mismatch repair defects.

Cancers with ‘mismatch repair’ gene mutations can’t correct single-letter mistakes in their DNA code properly and so are genetically unstable.

They acquire more and more mutations as they grow and rapidly evolve drug resistance – which is why new treatment approaches are so badly needed.

But the researchers suspected these ultra-mutant cancer cells might be particularly easy for the immune system to recognise, since they will look different from healthy cells.

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