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

Dr Mateo is investigating how to predict the worst prostate cancer cases by studying a group of genes involved in the cells’ DNA repair system.

Some patients with advanced prostate cancer have one or more changes to the genes responsible for repairing damaged DNA within their cancer cells. An example of these are the BRCA1 and BRCA2 genes, where a mutation to one of these genes is more likely to lead to a more aggressive form of prostate cancer, which is likely to progress much quicker and have a worse outcome.

A class of drugs – called PARP inhibitors - are currently in development to treat men with these genetic changes in their DNA repair system. This research project aims to determine just how frequently these defects to the DNA repair genes occur in prostate cancers and whether these mutations correspond with a patient’s response to treatment. They will then treat men with a PARP inhibitor and determine whether their response to treatment is linked to the presence or absence of genetic modifications to their DNA repair system. Following this, Dr Mateo aims to develop a simple test that may predict if a patient is likely to benefit from treatment with PARP inhibitors, which in due course will be tested in a larger-scale clinical trial.

What have they done so far?

During the first year of the project, Dr Mateo and his colleagues have completed a clinical trial testing a particular PARP inhibitor, called olaparib, in patients with advanced prostate cancer. Using samples from this study, they have identified that almost every patient who responded to this drug has changes in at least one gene involved in repairing damage to DNA. Conversely, patients who did not benefit from treatment with this PARP inhibitor were less likely to have modifications to these genes.

Next, the researchers intend to run a second clinical trial to test the drug olaparib in more patients. This time the patients will be selected to be treated with this drug based on the genetic modifications the researchers found. After this, they will investigate the effectiveness of this drug at an earlier stage of the disease.

Grant information

Reference - MRC-CRTF13-001
Researcher - Dr Joaquin Mateo
Institution - Institute of cancer Research
Award - £248,847