Navigation Links
Cleveland Clinic researcher finds genetic mutation in castration-resistant prostate cancer

AUG. 29, 2013, Cleveland:

The mutation occurs in the androgen-synthesizing enzyme 3βHSD1 in castration-resistant prostate cancer (CRPC), according to research published online today in Cell. This mutation enables the tumor to make its own supply of androgens, a hormone that fuels the growth of the prostate cancer.

Prostate cancer requires a constant supply of androgens in order to sustain itself. The current standard of care for patients with metastatic prostate cancer is medical castration, the ability to interfere with the body's production of testosterone (androgens) using medications that disrupt the process. Oftentimes, metastatic prostate cancer flourishes despite the lack of testosterone in the bloodstream, creating CRPC. These tumors are able to exist without the body's supply of testosterone by creating androgens within the tumor cell; however, increased androgen synthesis has not yet been attributable to any known mutations. The Cleveland Clinic discovery shows that the 3βHSD1 mutation makes this enzyme hyperactive to create androgens.

"This discovery gives us the ability to identify molecular subtypes of prostate cancer known to resist treatment. By finding the mutated enzyme, we can now investigate treatments that block it. This kind of strategy is the crux of personalized medicine which is currently used as the standard of care for some forms of lung cancer and melanoma," said Nima Sharifi, M.D., Kendrick Family Chair for Prostate Cancer Research at Cleveland Clinic, who led the research.

The 3βHSD1 mutation can occur within CRPC tumors and it can also come from germline DNA, which is inherited from maternal and paternal sources.

The research found that laboratory models of human prostate cancer fall into two categories of androgen synthesis: those that make androgens slowly and those that do so rapidly. Next, they found that the 3βHSD1 mutation explains the difference between these two categories and that DNA from some patient tumors also contains this mutation. The mutation works by opening the floodgates to androgen synthesis, essentially throwing fuel on the fire that promotes tumor progression.

In an era of personalized cancer care, there is increased focus on defining and treating cancer by its genetic abnormalities. Tumor-promoting enzyme mutations in several cancers have been identified and, subsequently, have led to the development of targeted drug therapies, improving outcomes for patients.

"The past decade has seen an explosion of molecularly targeted therapies that are matched to specific mutations in a given patient's tumor," says Dr. Sharifi. "However, no drug-targeting based on enzyme mutations exists for the standard treatment of metastatic CRPC. With this finding, we have the opportunity for matching a mutant disease-driving biomarker with a pharmacologic inhibitor."

Prostate cancer is the most common cancer in men, with nearly 240,000 new cases diagnosed each year in the United States. According to the American Cancer Society, there will be an estimated 30,000 deaths due to prostate cancer in 2013. Almost every man who dies of prostate cancer dies with castration-resistant prostate cancer.


Contact: Stephanie Jansky
Cleveland Clinic

Related medicine news :

1. CE Lectures on the Dental Treatment of Snoring and Sleep Apnea Include Rochester, Cleveland and Ft. Lauderdale, as Sleep Seminar Destinations
2. Cleveland Indians vs. Detroit Tigers Tickets: Cheap Concert Tickets Slashes Prices on All Indians vs. Tigers Tickets for August 5th - August 8th Series Progressive Field
3. National Transitions of Care Coalition to Host Regional Summit in Cleveland
4. Maroon 5 & Kelly Clarkson Ticket Prices Slashed for Concerts in Long Island, Holmdel, Cincinnati, Pittsburgh, Camden/Philly, Boston/Mansfield, Chicago, Cleveland & Detroi
5. Explorys Proud to Sponsor Cleveland GiveCamp
6. NEONI Participates in Healthcare Career Event at Cleveland Convention Center Grand Opening
7. Cleveland Clinic Laboratories to provide testing and diagnostic services to ACL Laboratories
8. Book of Mormon Tickets: Prices Slashed on Book of Mormon Tickets in New York, Chicago, Cleveland, Buffalo, Washington DC, Minneapolis, Houston and San Antonio
9. Cancer Survivor David Emerson Awarded Volkswagen Cup at Cleveland Marathon
10. Nine Inch Nails Tickets (NIN) Tickets Go On Public Sale for St. Paul, Toronto, Cleveland, Detroit, Boston, Brooklyn, Newark, Washington DC, Las Vegas, Portland on June 14th
11. Justin Timberlake Tickets: Cheap Concert Tickets Announces that Justin Timberlake Tickets Go Onsale 6/3 for Concerts in Omaha, St. Paul, Fargo, Pittsburgh, Cleveland, Indianapolis and St. Louis
Post Your Comments:
(Date:11/24/2015)... ... ... Charitable giving is at its peak during the holidays. In fact, ... the year totalling over $358 billion in 2014. With more than 1.5 million ... individuals who want to “give back” during the holidays. , “With so many charities ...
(Date:11/24/2015)... ... November 24, 2015 , ... In an article ... variables that determine which patients are or are not eligible for bariatric surgery. The ... BMI over 40, are more than 100 pounds overweight, or have a BMI of ...
(Date:11/24/2015)... ... ... DMG Productions announced that they will feature Aphria, Inc., in an upcoming episode ... and show times TBA. , Aphria, Inc., is a publicly traded company incorporated under ... medical marijuana pursuant to the Marijuana for Medical Purposes Regulations (the “MMPR”). , Aphria ...
(Date:11/24/2015)... ... ... Preparing for the LDT Regulation:, CLIA Won’t Satisfy the FDA, Dec. ... has long asserted that design and manufacture of Laboratory Developed Tests (LDTs) falls under ... the device regulations. , Come up short in an inspection and the FDA can ...
(Date:11/24/2015)... ... November 24, 2015 , ... ... organization will waive paid entry and parking fees at several of their most ... Mountain in Great Barrington in support of REI’s Black Friday #OptOutside Campaign. The ...
Breaking Medicine News(10 mins):
(Date:11/25/2015)... Nov. 25, 2015 USP 800 applies ... preparations (e.g. pharmacists, pharmacy technicians, nurses, physicians, physician ... The chapter also covers all entities which store, ... hospitals, other healthcare institutions, patient treatment clinics, physicians, ... --> --> What is the ...
(Date:11/25/2015)... Nov. 25, 2015  Mindray Medical ... MR ), a leading developer, ... worldwide, today announced that it will ... of shareholders at the Company,s Hong Kong office ... Prince Edward West Road, Mongkok KL, Hong ...
(Date:11/25/2015)... 2015 Research and Markets ( ) ... - Global Forecast to 2020" report to their ... for 37.21% of the total market share in 2014. ... region is projected to growth at the highest CAGR ... primarily to the fast growing water, industrial gas treatment, ...
Breaking Medicine Technology: