Testing for genetic weaknesses in repairing DNA could pick out men who may benefit from a new type of targeted nuclear medicine, a new study reports.
An emerging class of drugs are 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.
These new ‘search-and-destroy’ treatments are starting to show promise even in men with prostate for whom targeted treatments and chemotherapies have stopped working閳ユ攤ut not all patients respond.
In the new study, scientists at The Institute of Cancer Research, London, 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 study is published in the journal European Urology today (Tuesday), and was funded by the Movember Foundation, Prostate Cancer UK, Cancer Research UK and the Prostate Cancer Foundation.
The researchers analysed tumour samples from men with 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閳ユ攣 protein molecule called prostate-specific membrane antigen, or PSMA閳ユ敋as 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.
But 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.
That 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閳ユ攩ollowed by having tumours scanned using PSMA imaging technology.
The researchers believe that PSMA plays a key role in keeping the genome in cells stable閳ユ攣nd could be produced by tumours as a survival mechanism where they are defective in repairing their DNA. This could explain the link between DNA repair faults and high levels of PSMA.
These findings also suggest that with other drugs that increase genetic instability could make prostate tumours more likely to respond to PSMA-targeting treatments.
Next, the researchers aim to 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.
Precise targeting of cancer cells and use of drug combinations are among a range of strategies being pursued at The Institute of Cancer Research (ICR) through its new Centre for Cancer Drug Discovery.
The ICR閳ユ攣 charity and research institute閳ユ攰s raising the final 鎷
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