CAUTION, some doctors use estrogen patches as a form of first line hormone blockade therapy for the treatment of prostate cancer. However, scientists from Weill Cornell Medical College, New York City have described the hormone estrogen as a potential key negative player in about half of all prostate cancers.
Researchers have found that Estrogen-linked signaling helps drive a discrete and aggressive form of prostate cancer which is caused by a chromosomal translocation, which in turn results in the fusion of two genes. “Fifty percent of prostate cancers harbor this common recurrent gene fusion, and we believe that this confers a more aggressive nature to these tumors,” explains study senior author Dr. Mark A. Rubin, professor of pathology and laboratory medicine, and vice chair for experimental pathology.
Dr. Rubin suggested that an eventual treatment goal for many prostate cancers would be the interference with this particular gene fusion. He went on to say that, he believed that inhibiting estrogen might be one way to prevent this gene fusion, which would impact many aggressive prostate cancer tumors.
The study findings were published in the May 27 online edition of the Journal of the National Cancer Institute. Dr. Rubin, along with his team is now continuing this line of research.
Some history- Dr. Rubin, along with researchers at the University of Michigan, demonstrated that there is a common fusion between the TMPRSS2 and ETS genes in a large subset of prostate cancer patients. These genetic fusions are characterized as a fusion of an androgen (male hormone)-dependent gene fusing with an oncogene (a type of gene that causes cancer).
Prostate cancer has many genetic pathways through the human body. A traditional hormone blockade using a LHRH inhibitor will only work for a limited time. At some point, the blockade stops working and levels of testosterone will increase along with prostate cancer progression. The prostate cancer has developed an alternative pathway, circumventing the LHRH inhibitor.
Researchers performed an analysis of 455 prostate cancer samples from trials in Sweden and the United States. The close analysis of the genetic signatures of the samples yielded a surprise: that estrogen-dependent molecular pathways appear to play a crucial role in regulating (and encouraging) an aggressive subset of prostate cancer.
Men naturally produce levels of estrogen, even though we think of estrogen as being a female hormone. “Now, we show for the first time that this natural estrogen can stimulate the production of the cancer-linked TMPRSS2-ERG fusions, via the estrogen receptor (ER)-alpha and ER-beta. These receptors are found on the surface of some prostate cancer cells,” Dr. Rubin explains. Dr. Rubin and his colleagues feel that the presence of the estrogen encourages the genetic fusion and the progression of an aggressive tumor.
The finding could have implications for prostate cancer research, including future drug development. According to Dr. Rubin, “We now believe that agents that dampen estrogen activity (ER-beta antagonists) could inhibit fusion-positive prostate cancers. Alternatively, any intervention that boosts estrogen activity (ER-alpha) might also give a boost to these aggressive malignancies.”
As with breast cancer, prostate cancer probably can be divided into cancers that either are or not influenced by estrogen. Using estrogen as a hormone blockade might in fact feed the aggressiveness of some prostate cancers.
This work was funded by the U.S. National Institutes of Health, a Prostate SPORE grant at the Dana-Farber/Harvard Cancer Center, Swiss Foundation for Medical-Biological Grants SSMBS, U.S. Department of Defense and the Prostate Cancer Foundation.
Co-researchers include study co-lead authors Dr. Sunita Setlur and Dr. Kirsten Mertz of Brigham and Women’s Hospital and Harvard Medical School, Boston; Dr. Yujin Hoshida and Dr. Todd Golub of the Broad Institute and the Dana-Farber Cancer Institute, Boston; Dr. Francesca Demichelis of Weill Cornell Medical College and Harvard Medical School, Boston; Dr. Mathieu Lupien of the Dana-Farber Cancer Institute; Dr. Sven Perner and Jeff Tang of Weill Cornell Medical College; Andrea Sboner of Yale University, New Haven; Dr. Yudi Pawitan and Dr. Katja Fall of the Karolinska Institutet, Stockholm, Sweden; Dr. Ove Andren, Dr. Jan-Erik Johansson and Dr. Swen-Olof Andersson, of Orebro University Hospital, Orebro, Sweden; Laura A. Johnson of Brigham and Women’s Hospital, Boston; Dr. Hans-Olov Adami, of Karolinska Institutet, Sweden, and Harvard School of Public Health, Boston; Dr. Stefano Calza, of the Karolinska Institutet, Sweden, and the University of Brescia, Italy; Dr. Arul M. Chinnaiyan, Dr. Daniel Rhodes and Scott Tomlins, of the University of Michigan Medical School, Ann Arbor; Dr. Lorelei Mucci and Dr. Meir Stampfer of Harvard Medical School, Harvard School of Public Health and Brigham and Women’s Hospital, Boston; Dr. Philip Kantoff of Dana-Farber Cancer Institute and Harvard Medical School; Dr. Eberhard Varenhorst, of University Hospital Linkoping, Sweden; and Dr. Myles Brown of the Dana-Farber Cancer Institute.
Dr. Mark A. Rubin, Dr. Francesca Demichelis, Dr. Sven Perner, Dr. Arul M. Chinnaiyan and Scott Tomlins are co-inventors on a patent filed by the University of Michigan and the Brigham and Women’s Hospital, covering the diagnostic and therapeutic fields for ETS fusions in prostate cancer.
Joel T Nowak MA, MSW