In The News

Well-Done Meat Consumption May Increase Prostate Cancer Risk
Research into the dietary habits of about a thousand men from the Cleveland area has found that a high consumption of meats, especially of red meat prepared by grilling, is positively associated with an increased risk of developing aggressive prostate cancer. This particular study, which was led by Dr. John Witte of the University of California, San Francisco (UCSF), has a number of limitations, but it does add support to other investigations connecting meat consumption with cancer risk.

Toronto researchers speculate regarding a link between prostate cancer and oral contraceptive use
Very preliminary and speculative research, designed to spark further inquires, suggests that there may be a connection between oral contraceptive use and rising rates of prostate cancer. One theory is that the widespread use of birth-control pills in various populations may result in a higher level of estrogen in the environment, which might, in turn, increase prostate cancer risk.

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New Pathway Discovered to Possible Treatment of Advanced Prostate Cancer

8/1/2011

Researchers from the University of Texas Southwestern Medical Center have demonstrated that the growth of advanced prostate cancer resistant to standard hormonal therapy, also known as castration resistant prostate cancer (CRPC), is driven by a different hormonal pathway than was thought previously.

We have known for a long time that the male hormone testosterone stimulates the growth of prostate cancer. This knowledge is the basis of current hormone therapy, which deprives prostate cancer cells of the male hormones (androgens) that they need to flourish. However, we also know that, over time, prostate cancer can become resistant to this therapy. In other words, it will grow in spite of being deprived of testosterone.

What researchers at UT Southwestern have discovered is that hormone resistant prostate cancer is driven by a pathway that circumvents the male hormone testosterone. As lead researcher Dr. Nima Sharifi explains it, “The general assumption is that the tumour accelerates through testosterone when, in fact, the pathway goes around it to the most potent hormone.” He continues, “We both found the existence of this pathway in models and patients and have shown that these resistant tumours are clearly driven by this other pathway.”

In slightly more scientific terms, the discovery can be described this way. A tumour becomes hormone resistant when it begins to make its own potent androgen (or male hormone), specifically, DHT or dihydrotestosterone. This androgen is normally synthesized in the prostate, testes, hair follicles, and adrenal glands by 5α-reductase, an enzyme that reduces the hormone testosterone to form the more potent androgen dihydrotestosterone. In castration resistant prostate cancer, the synthesis of DHT is widely assumed to require the 5α-reduction of testosterone as its precursor, and the increased expression of steroid-5α-reductase isoenzyme-1 (SRD5A1) over SRD5A2 is thought to reflect its role in converting testosterone to DHT. The researchers show, however, that the dominant route of DHT synthesis in hormone resistant tumours bypasses testosterone and instead requires the 5α-reduction of androstenedione by SRD5A1 to 5α-androstanedione, which is then converted to DHT.

This discovery has significant implications for the development of new treatments. In fact, it reframes the fundamental metabolic pathway that drives the progression of advanced, hormone resistant prostate cancer. “This now suggests that a potential drug target is one step upstream in the pathway,” reports Dr. Sharifi. “This can be thought of as charting a map of the correct pathway. You have to figure out which way the river flows before you can block the river.”

Another potential benefit stemming from this discovery is the development of accurate indicators of response or resistance to hormonal therapy. These biomarkers may eventually help doctors identify why and exactly how tumours become hormone resistant.

“Our findings will change the framework for the way people think about this disease,” summarizes Dr. Sharifi.

References:
Kai-Hsiung Changa, Rui Lia, Mahboubeh Papari-Zareeib, Lori Watumullc, Yan Daniel Zhaod, Richard J. Auchusb, and Nima Sharifi, 27 July 2001 (pre-publication online), Dihydrotestosterone synthesis bypasses testosterone to drive castration-resistant prostate cancer, Proceedings of the National Academy of Sciences of the United States of America.

UT Southwestern Medical Center, 25 July 2011, UT Southwestern scientists discover new pathway to potential therapies for advanced prostate cancer, UT Southwestern Medical Center News Releases.