A new test which tests for genetic weaknesses in repairing DNA can pick out prostate cancer patients who could benefit from a ‘search-and-destroy’ type medicine.
The targeted nuclear medicine, which is part of an emerging class of drugs, is made up of a radioactive particle that can kill cells attached to a ‘homing device’ to seek out cancers by detecting the presence of a target molecule on their surface.
The treatments are starting to show promise even in men with prostate cancer for whom targeted treatments and chemotherapies have stopped working – but not all patients respond.
In a recent study scientists at The Institute of Cancer Research found that testing men for faults in DNA repair genes in their tumours could identify those most likely to respond to the new type of treatment.
The researchers analysed tumour samples from men with advanced prostate cancer who had been treated at The Royal Marsden NHS Foundation Trust, in order to try to understand why the response to search-and-destroy treatment varied.
They found that the target for these new treatments – a protein molecule called prostate-specific membrane antigen (PSMA) – was present at higher levels on the surface of cancer cells in some patients than others. PSMA levels even varied substantially between different cancer sites in the same patient.
Crucially, the amount of PSMA on the surface of cancer cells was more than four times higher in tumours where there were also faults in DNA repair genes, which means that testing for genetic faults in DNA repair genes could be used as a first-stage screen to select patients for PSMA-targeted treatment – followed by having tumours scanned using PSMA imaging technology.
Professor Johann de Bono, regius professor of cancer research at the ICR explained that the study “helps to explain why some patients respond to search-and-destroy treatments and others don’t. Understanding the biology of response to these new treatments is critical to getting them into use in the clinic as soon as possible.”
He continued, “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.”
Researchers will now assess whether testing for DNA repair faults can effectively target search-and-destroy treatment as part of clinical trials, and to explore combination strategies to see if the response to these treatments could be heightened.