A new study by The Institute of Cancer Research, London (ICR) has shown that a genetic test for faults in DNA repair could enable targeted nuclear treatments for patients with prostate cancer.
The ‘search-and-destroy’ drugs contain a radioactive particle that can identify a target molecule on the surface of cancer cells called prostate-specific membrane antigen (PSMA).
This new approach was found to be effective in prostate cancer patients who did not experience an adequate response to targeted treatments and chemotherapies. However, it does not work for all patients.
During the latest study, researchers observed that information on weaknesses in DNA repair genes could help to determine which patients would be most likely to respond to the search-and-destroy treatment.
Analysis of advanced prostate cancer samples revealed higher levels of PSMA on the surface of cancer cells in certain men. Additionally, the levels of protein varied at different cancer sites within the same patient.
It was further observed that the PSMA was more than four times higher in tumours with faults in DNA repair genes.
Based on these findings, the researchers concluded that a genetic test for DNA repair weaknesses could act as a first-stage screen to identify patients for PSMA-targeted therapy.
Moreover, the team believes that combination therapy that boosts genetic instability could increase the chance of PSMA-targeting treatment response.
ICR cancer research professor Johann de Bono said: “We found that testing for DNA repair defects was a good indication of which tumours had high levels of PSMA, and so would be expected to respond to these PSMA-targeted therapies.
“We will need to further assess the use of DNA tests to target these treatments effectively in routine care, but we can already now start to take into account DNA repair faults in our design of clinical trials.”
The researchers plan to evaluate the new genetic test in clinical trials, as well as identify combination treatments to boost therapy response.