Deadlier subtype of metastatic prostate cancer found to be common than previously thought

A new study of prostate cancer in 202 men, whose cancers had spread and were resistant to standard treatment, found that a surprisingly large number of these cancers – about 17 percent – belong to a deadlier subtype of metastatic prostate cancer.

Previously, it was thought that these cancers constituted less than 1 percent of all prostate cancers.

The study, which was led by researchers at UC San Francisco and published online July 9 in the Journal of Clinical Oncology, suggests that this prostate cancer subtype, called treatment-emergent small cell neuroendocrine prostate cancer (t-SCNC), might in the future be routinely and more successfully treated with targeted drugs that already are being developed or tested in clinical trials.

"Think of advanced, hormone-treatment-resistant prostate cancers as a pie," said Rahul Aggarwal, MD, assistant professor of medicine in the UCSF Division of Hematology and Oncology and the study's corresponding author. "Instead of treating these advanced cases homogenously as we do with today's standard treatments, we want to split the pie according to tumor characteristics, and develop treatment protocols tailored to individual slices, based on the cancers' distinctive growth-driving genetic mutations and gene expression patterns."

The research team identified specific genetic mutations and patterns of gene expression that are found in t-SCNC, but are distinct from the more common type of prostate cancer known as adenocarcinoma. Among the patterns identified in t-SCNC was higher activity of specific "transcription factor" proteins – proteins that switch on production of other proteins that drive cancer growth.

Two of the transcription factors over-activated in t-SCNC are targets of drugs already in clinical trials, Aggarwal said, with several more in pre-clinical testing. Aggarwal is a member of the UCSF Helen Diller Family Comprehensive Cancer Center.

In contrast, mutations that previously have been discovered to play a role in many adenocarcinomas were almost never present in t-SCNC, the researchers found.

Treatments targeting specific mutations in prostate cancer are not yet available in standard practice, which relies on hormonal treatment and chemotherapy as the mainstays of treatment. However, as the number of targeted treatments available for cancer grows, genetic analysis of tumors is expected to become increasingly valuable in helping to guide treatment.

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