In a new study, researchers found that testing for genetic weaknesses in repairing DNA could pick out men who may benefit from a new type of targeted nuclear medicine.
Nuclear medicine is made up of a radioactive particle that can kill cells attached to a ‘homing device’ to seek out cancers.
The research was conducted by a team from The Institute of Cancer Research, London.
These new ‘search-and-destroy’ treatments are starting to show promise even in men with prostate cancer for whom targeted treatments and chemotherapies have stopped working.
In the new study, the team found that testing men for faults in DNA repair genes in their tumors could identify those most likely to respond to the new type of treatment.
The researchers analyzed tumor samples from men with advanced prostate cancer to find which patients may benefit from the new treatment.
They found that the target for these new treatments—a protein molecule called prostate-specific membrane antigen, or PSMA—was present at higher levels on the surface of cancer cells in some patients than others.
The amount of PSMA on the surface of cancer cells was more than four times higher in tumors where there were also faults in DNA repair genes.
PSMA levels were varied between different cancer sites in the same patient.
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—followed by having tumors scanned using PSMA imaging technology.
The researchers believe that PSMA plays a key role in tumors 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 combination therapy with other drugs that increase genetic instability could make prostate tumors more likely to be killed by the new treatment.
The team will need to further assess the use of DNA tests to target these treatments effectively in routine care.
One author of the study is Professor Johann de Bono, Regius Professor of Cancer Research.
The study is published in the journal European Urology.
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