Drugs being tested in clinical trials may target growth-fuelling proteins in a lethal form of aggressive prostate cancer, a study has found.
A deadly form of aggressive prostate cancer may be far more common than was previously thought, research suggests.
Scientists who studied 202 men whose cancers had spread and were resistant to standard treatment found that 17% had the deadly subtype. Previously it was thought that the strain accounted for less than 1% of all prostate cancers.
However, the same study offered a glimmer of hope for men with the subtype, known as treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC). It found that t-SCNC tumours contained two growth-fuelling proteins that could be targeted by drugs now being tested in clinical trials.
Dr. Rahul Aggarwal, one of the US researchers from the University of California at San Francisco (UCSF), assistant professor of medicine in the UCSF Division of Hematology and Oncology and one of the study’s authors, said: “We want to know why prostate cancer becomes resistant, and we believe the emergence of t-SCNC is one important mechanism through which they evolve and evade treatment.”
The study found that t-SCNC cancers had mutations that led to the over-production of certain proteins that drove cancer growth. Among them were two “transcription factors” – molecules that switch on the production of other proteins – already being targeted in clinical trials.
Other mutations previously shown to play a role in many “normal” cancers were almost never present in the t-SCNC subtype.
The findings, published in the Journal of Clinical Oncology, suggest that this kind of cancer could be more successfully treated with targeted drugs.
“Think of advanced, hormone-treatment-resistant prostate cancers as a pie,” said Dr. Rahul Aggarwal. “Instead of treating these advanced cases homogeneously as we do with today’s standard treatments, we want to split the pie according to tumor characteristics.”
All the men taking part in the study had stopped responding to the advanced second-line hormone treatment drugs abiraterone and enzalutamide. Biopsy samples showed that 27 out of 160 men had t-SCNC cancers. They survived 36.6 months on average compared with 44.4 months for patients without the subtype.
Co-author Professor Eric Small, head of hematology and oncology at the UCSF, said: “An understanding of the biology of this important mechanism of resistance is essential to our developing novel therapeutics designed to prevent the development of this lethal prostate cancer subtype, or, once developed, to effectively treat it.”
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Deadly form of advanced prostate cancer is common, calls for distinct treatment
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