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Researchers find new culprit in castration-resistant prostate cancer
Date:12/13/2012

BOSTONScientists at Dana-Farber Cancer Institute have discovered a molecular switch that enables advanced prostate cancers to spread without stimulation by male hormones, which normally are needed to spur the cancer's growth. They say the finding could lead to a new treatment for prostate cancers that are no longer controlled by hormone-blocking drugs.

The researchers report in the Dec. 14 issue of Science that the molecular switch occurs in a protein, EZH2, which is increased in these tumors, termed castration-resistant prostate cancers (CRPC).

EZH2 is part of a protein complex that normally shuts off the expression of genes. But in CRPC cells, "It isn't working the way people had thought," said Myles Brown, MD, co-senior author of the report. Instead, EZH2 switches into a different mode, activating cell-growth genes -even in the absence of androgen hormones that spur the dangerous growth and spread of these cancers.

As a result, the researchers suggest that drugs designed to stifle this unexpected function of EZH2 might be effective as a new treatment strategy for CRPC tumors.

Brown's co-senior author is X. Shirley Liu, PhD; together they lead Dana-Farber's Center for Functional Cancer Epigenetics.

Most prostate tumors are fueled by male hormones, or androgens, which interact with a molecule called the androgen receptor in cancer cells. When the receptor receives androgen signals, it transmits orders to the cell's nucleus to divide and grow. Surgical castration or administering drugs that halt androgen production can control cancers that have spread outside the prostate gland.

However, these cancers often escape their need for androgens after a few years of treatment and become resistant. Brown said the tumor cells reprogram the androgen receptors so that they activate cell-growth genes despite the absence of hormone stimulation.

EZH2 is known as an "epigenetic regulator," meaning that
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Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

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