Navigation Links
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 it regulates the activity of genes without changing their DNA structure. Previously it was found that EZH2 levels are dramatically increased in late-stage castration resistant prostate cancer, Brown said, but researchers thought the protein was acting primarily to turn off gene activity which is its normal role.

Drugs aimed at blocking EZH2 activity are being tested in other cancers, where they are designed to block the protein's gene-suppressing role. However, they carry a risk of harmful side effects as a result. "But we found that isn't the important function of EZH2 in CRPC," Brown explained. "In these cancers, EZH2 works with the androgen receptor to turn on genes involved with cell growth." As a result, he proposes that inhibitors of EZH2 that avoid targeting its gene-repressor function might be a safe and effective strategy for use in castration-resistant prostate cancers.

Further, said Brown, the EZH2 protein itself is activated by a molecular signaling pathway known as PI3K, or PI3 kinase. Several PI3K inhibitors are in clinical trials at present, and Brown said that a combination of drugs to inhibit both that pathway and the EZH2 protein might be yet another way to attack the resistant prostate cancers.


'/>"/>

Contact: Bill Schaller
william_schaller@dfci.harvard.edu
617-632-5357
Dana-Farber Cancer Institute
Source:Eurekalert  

Related biology news :

1. ASU researchers propose new way to look at the dawn of life
2. New geometries: Researchers create new shapes of artificial microcompartments
3. UGA researchers find algal ancestor is key to how deadly pathogens proliferate
4. Researchers identify new components of the epigenetic code for honey bee development
5. Researchers find new genetic pathway behind neurodevelopmental disorders
6. Researchers investigate impacts of climate change on rare tropical plants
7. Researchers identify proteins that indicate which kidney tumors are most likely to spread
8. Microchoreography: Researchers use synthetic molecule to guide cellular dance
9. Einstein researchers receive 2 Grand Challenges Explorations grants to combat HIV and TB
10. University of Tennessee researchers find fungus has cancer-fighting power
11. UC Davis researchers aid effort to sequence the complex wheat genome
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Researchers find new culprit in castration-resistant prostate cancer
(Date:2/2/2016)... MOUNTAIN VIEW, Calif. , Feb. 2, 2016 ... diabetic retinopathy market, Frost & Sullivan recognizes US-based ... North America Frost & Sullivan Award for New ... technology provider in North America ... standard in the rapidly growing diabetic retinopathy market. ...
(Date:2/1/2016)... 1, 2016  Wocket® smart wallet ( www.wocketwallet.com ) announces the launch ... Joey Fatone . Las Vegas , where Joey ... --> Las Vegas , where Joey appeared at the ... new video ad was filmed at the Consumer Electronics Show (CES2016) in ... booth to meet and greet fans. --> ...
(Date:1/25/2016)... BLUE BELL, Pa. , Jan. 25, 2016   Unisys ... facial recognition system at John F. Kennedy (JFK) International Airport, ... and Border Protection (CBP) identify imposters attempting to enter ... or do not belong to them. pilot testing ... rolled out initially at three terminals at JFK during January 2016. ...
Breaking Biology News(10 mins):
(Date:2/3/2016)... ... February 03, 2016 , ... ... annual report which summarizes and analyzes nearly 750 unique supply chain notifications ... and analysis service. , Supply chain risk management practitioners subscribe to the ...
(Date:2/3/2016)... , Feb. 3, 2016  Today, Symphony Technology ... AlphaImpactRx , a leading provider of primary research ... to IMS Health , a global information and ... offerings, capabilities and technologies will be integrated into IMS ... global primary market research capabilities. ...
(Date:2/3/2016)... MN (PRWEB) , ... February 03, 2016 , ... ... physiologic monitoring, has released two new solutions focused on social housing of small ... and reduces stress artifacts in data.¹, ² , DSI’s HD-S11 implant has evolved ...
(Date:2/3/2016)... , ... February 03, 2016 , ... Big games come ... have sacrificed so much for our country. CereScan, a nationally recognized brain diagnostics and ... Wounded Warrior Amputee Football Team (WWAFT) vs. NFL Stars Flag Football Game on February ...
Breaking Biology Technology: