Treatment of prostate cancer patients with changes to their DNA repair genes

Grant information

Institution – The Institute of Cancer Research, London.
Researcher – Dr Joaquin Mateo
Grant award - £250,863
Duration of funding – 2014-2017
Status - Complete
Reference – MRC-CRTF13-001

Why did we fund this project?

• Some men with advanced prostate cancer have changes, called mutations, in the genes that repair damage to DNA. For example, mutations in the BRCA genes are linked with aggressive prostate cancer. Men with mutations in DNA repair genes may be more likely to respond to specific types of treatment.
• Dr Joaquin Mateo wanted to find out how often these mutations occur in men with advanced prostate cancer and whether these mutations make men more likely to respond to a type of drug called PARP inhibitors.
• It was hoped that this project would contribute towards the identification of a new, personalised therapy option for advanced prostate cancer so that each man gets the treatment that is right for them.

What did the researcher do?

• Firstly, over 150 prostate cancer samples donated by men were analysed in the laboratory to work out if they had mutations in genes involved in repairing DNA damage.
• Then, Dr Joaquin Mateo looked to see if men who responded well to treatment with a PARP inhibitor drug called olaparib had mutations in their DNA repair genes.

What did the researcher achieve?

• It was observed that approximately 32% of the analysed samples had mutations in DNA repair genes, with BRCA2 being the most commonly affected gene.
• Notably, this project identified that on many occasions the mutations have been inherited – further highlighting why men are more at risk if their dad or brother had prostate cancer.
• Excitingly, research showed that men with mutations in DNA repair genes benefited most from olaparib.

How will this benefit men?

• Therapies for men with advanced prostate cancer are limited - new, personalised treatment options are urgently needed.
• This project provided crucial evidence required to launch international clinical trials testing olaparib in large numbers of men with prostate cancer that has stopped responding to hormone treatment.
• Importantly, this research contributed towards a change to clinical practice recommendations on testing for inherited mutations. This testing means that men with BRCA mutations can now be treated with olaparib.