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Test to identify men who can benefit from medicine "search and destruction"
Adrian O & # 39; Dowd
Tuesday, July 23, 2019
The search for genetic weaknesses in DNA repair could help identify men likely to benefit from a new type of targeted nuclear medicine, suggests a study * published today in the journal European urology.
An emerging clbad of drugs consists of a radioactive particle that can kill cells attached to a "homing device" to detect 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 cancer for whom targeted therapies and chemotherapy have stopped working, but not all patients respond.
In this new study, scientists at the Institute of Cancer Research in London discovered that looking for defects in the DNA repair genes of tumors in men would identify those who are most likely to react to the new type of treatment.
The study was funded by the Movember Foundation, Prostate Cancer UK, Cancer Research UK and the Prostate Cancer Foundation.
The researchers badyzed tumor samples from 38 men with advanced prostate cancer who had been treated at the Royal Marsden NHS Foundation Trust, to understand why the response to "search and destroy" treatment varied.
They discovered that the target of these new treatments – a protein molecule called prostate specific antigen (PSMA) – was present at higher concentrations on the surface of cancer cells in some patients. The levels of PSMA varied even considerably 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 tumors also showing defects in DNA repair genes.
This means that screening for genetic defects in DNA repair genes could be used as a first-stage screening to select patients for targeted treatment with PSMA, followed by a digitization of tumors using the technology. PSMA imaging.
The researchers believe that PSMA plays a key role in genome stability in cells and could be produced by tumors as a survival mechanism in which they do not repair their DNA.
These results also suggest that combination therapy with other drugs increasing genetic instability could make prostate tumors more likely to respond to treatments targeting PSMA.
The researchers said they were now considering whether screening for DNA repair defects could effectively target the search and destruction treatments in clinical trials, and to find out more about the potential of DNA repair. explore combination strategies to see if the response to these treatments could be increased.
The precise targeting of cancer cells and the use of drug combinations are part of the strategies implemented at the Cancer Institute in London, through its new Center for Cancer Drug Discovery.
Professor Johann de Bono, Regional Professor of Cancer Research at the Institute and Consultant in Oncology at the Royal Marsden NHS Foundation Trust, said, "Our new study helps explain why some patients respond to search and destruction treatments. and others not. . Understanding the biology of the response to these new treatments is essential to be able to use them as soon as possible in the clinic.
"We will have to further evaluate the use of DNA tests to effectively target these treatments in routine care, but we can already begin to take into account the DNA repair defects in our clinical trial design. "
* Paschalis A, et al. Protein specific membrane antigen heterogeneity and DNA repair defects in prostate cancer. Eur Urol (2019). DOI: 10.1016 / j.eururo.2019.06.030.
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