Estrogen helps drive aggressive form of prostate cancer

Estrogen-linked signaling helps drive a discrete and aggressive form of prostate cancer caused by a chromosomal translocation, which, in turn, results in the fusion of two genes, researchers report.

“Fifty percent of prostate cancers harbor a common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors,” said Mark A. Rubin, MD, Weill-Cornell Medical College, New York. “Interfering with this gene fusion-or its downstream molecular pathways-will be crucial in the search for drugs that fight the disease. Based on our new data, we now believe that inhibiting estrogen may be one way of doing so.”

The team analyzed 455 prostate cancer samples from trials in Sweden and the United States that were conducted as far back as the mid-1970s. To retrieve the genetic information, they developed an innovative technology for effectively “reading” the gene transcription profiles hidden in the samples. The team was able to obtain a robust, 87-gene expression “signature” that distinguishes fusion-positive TMPRSS2-ERG cancers from other prostate malignancies.

The findings, published online in the May 27 edition of the Journal of the National Cancer Institute, revealed that estrogen-dependent molecular pathways appear to play a crucial role in regulating and encouraging this aggressive subset of prostate cancer.

“We now believe that agents that dampen estrogen activity could inhibit fusion-positive prostate cancers,” Dr. Rubin said. “Alternatively, any intervention that boosts estrogen activity might also give a boost to these aggressive malignancies.”