Researchers find new culprit in castration-resistant prostate cancer
Scientists 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.
More information: "EZH2 Oncogenic Activity in Castration-Resistant Prostate Cancer Cells is Polycomb-Independent," by K. Xu; Science, 2012.
Journal reference: Science
Provided by Dana-Farber Cancer Institute
- Study reveals a reprogrammed role for the androgen receptor Jul 27, 2009 | not rated yet | 0
- Hormone refractory prostate cancers more likely to spread to other organs Feb 20, 2008 | not rated yet | 0
- Targeted cancer therapy kills prostate tumor cells Jun 06, 2011 | not rated yet | 0
- Researchers ID molecule linked to aggressive cancer growth, spread Nov 13, 2008 | not rated yet | 0
- Prostate cancer gets around hormone therapy by activating a survival cell signaling pathway Jun 14, 2011 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Why is zone 1 in liver more prone to ischemic injury?
May 23, 2013 Hi, Is it because around central vein, there is only deoxygenated blood from the vein where as in the periphery there is hepatic artery. Also why...
How can there be villous adenoma in colon, if there are no villi there
May 22, 2013 As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
- More from Physics Forums - Medical Sciences
More news stories
In recent years, microRNAs (miRNAs) and other non-coding RNAs are small molecules that help control the expression of specific proteins. In recent years they have emerged as disease biomarkers. miRNA profiles have been used ...
Cancer May 24, 2013 | not rated yet | 0
Cancer cells spread and grow by avoiding detection and destruction by the immune system. Stimulation of the immune system can help to eliminate cancer cells; however, there are many factors that cause the immune system to ...
Cancer May 24, 2013 | 5 / 5 (1) | 0
Researchers from London's Kingston University have begun a two-year study which could help prolong the lives of people with colorectal tumours.
Cancer May 24, 2013 | 5 / 5 (1) | 0
Transformative research from Western University has identified new hormones in the body which may suppress breast cancer and stimulate the regression of breast tumors.
Cancer May 24, 2013 | 5 / 5 (2) | 0
(Medical Xpress)—Curtin University researchers have found evidence that targeting specific cells in the body can reverse the effects of cancer on the immune system.
Cancer May 24, 2013 | 5 / 5 (4) | 0
(HealthDay)—Animals make great companions for senior citizens, but elderly people who always drive with a pet in the car are far more likely to crash than those who never drive with a pet, researchers have ...
3 hours ago | not rated yet | 0
Coenzyme Q10 decreases all cause mortality by half, according to the results of a multicentre randomised double blind trial presented today at Heart Failure 2013 congress. It is the first drug to improve heart failure mortality ...
11 hours ago | 5 / 5 (2) | 5
Heart failure accelerates the aging process and brings on early andropausal syndrome (AS), according to research presented today at the Heart Failure Congress 2013. AS, also referred to as male 'menopause', was four times ...
11 hours ago | not rated yet | 1
Mortality and length of stay are highest in heart failure patients admitted in January, on Friday, and overnight, according to research presented today at the Heart Failure Congress 2013. The analysis of nearly 1 million ...
11 hours ago | not rated yet | 0
(AP)—Department of Justice lawyers have again asked a federal appeals court in New York to delay lifting age restrictions and prescription requirements on an emergency contraceptive popularly known as the morning-after ...
11 hours ago | not rated yet | 0