Scientists solve key piece of prostate cancer puzzle

August 14, 2012, Cancer Research UK

Cancer Research UK scientists have revealed a completely new route by which male androgen hormones fuel the growth of prostate cancer, raising the prospect that existing drugs could be used to treat the disease.

Prostate cancers are often treated with hormone therapies that target the (AR) – a large protein that switches on signals telling the cell to divide, and which can become overactive in prostate cancer cells.

AR relies on interactions with several other proteins, such as HSP90 and p23, which help fold it into its active form.

Previously it was thought that p23 and HSP90 work together to activate AR, but this latest research – funded by Cancer Research UK and the Association for International Cancer Research – shows that p23 also increases activity of the AR independently.

Crucially this means that drugs to block p23 could be effective at treating prostate cancers that have become resistant to HSP90 inhibitors – which are currently being trialled in breast and prostate cancers.

The findings are published in Molecular Endocrinology.

Study leader, Dr Charlotte Bevan, from the Department of Surgery and Cancer at Imperial College London, said: “Cell signals from the androgen receptor (AR) drive many prostate cancers and our team is part of an ongoing international effort to find new targets that can potentially disable this key protein.

“Previously it was thought that HSP90 and p23 went hand in hand, so we were surprised to find that p23 was also able to boost the activity of the androgen receptor even when we used a modified form that was unable to bind HSP90.

“Excitingly, drugs that block p23 such as Celastrol, which is derived from a plant used in Chinese medicine, have shown early promise in treating several diseases, such as arthritis and asthma, meaning this research is already a step closer to the clinic. The next stage will be to test the effects of such drugs on prostate cancer cells in the lab.”

The researchers used antibodies specifically designed to target p23 to show that levels of the protein are higher in the nucleus of prostate cancer cells compared to normal cells. They also used a modified form of p23, unable to bind HSP90, to show that p23 can act independently of HSP90 and does not necessarily need the protein to interact with the AR.

Dr Julie Sharp, senior science information manager at Cancer Research UK, said: “These results provide an alternative route by which scientists could potentially target prostate cancer by halting AR activity. What’s more, p23 has a much more defined role in the cell than HSP90, meaning that drugs that target it could potentially have fewer side effects for patients than HSP90 inhibitors. We hope these findings will lead to better treatment options for men with .”

Explore further: Researchers discover that same gene has opposite effects in prostate, breast cancers

More information: Molecular Endocrinology June 28, 2012 me.2011-1360 doi: 10.1210/me.2011-1360

Related Stories

Researchers discover that same gene has opposite effects in prostate, breast cancers

October 17, 2011
Researchers at Cleveland Clinic have discovered that a gene – known as an androgen receptor (AR) – is found in both prostate and breast cancers yet has opposite effects on these diseases.

Study identifies new prostate cancer drug target

February 6, 2012
Research led by Wanguo Liu, PhD, Associate Professor of Genetics at LSU Health Sciences Center New Orleans, has identified a new protein critical to the development and growth of prostate cancer. The findings are published ...

A single therapy slows multiple cancers

January 23, 2012
Targeting a single protein can help fight both breast cancers and leukemias, according to two reports published online on January 23 in the Journal of Experimental Medicine.

Prostate cancer gets around hormone therapy by activating a survival cell signaling pathway

June 14, 2011
Cancer is crafty. When one avenue driving its growth is blocked by drugs targeting that path, the malignancy often creates a detour, finding an alternative route to get around the roadblock.

Recommended for you

Single blood test screens for eight cancer types

January 18, 2018
Johns Hopkins Kimmel Cancer Center researchers developed a single blood test that screens for eight common cancer types and helps identify the location of the cancer.

How cancer metastasis happens: Researchers reveal a key mechanism

January 18, 2018
Cancer metastasis, the migration of cells from a primary tumor to form distant tumors in the body, can be triggered by a chronic leakage of DNA within tumor cells, according to a team led by Weill Cornell Medicine and Memorial ...

Researchers find a way to 'starve' cancer

January 18, 2018
Researchers at Vanderbilt University Medical Center (VUMC) have demonstrated for the first time that it is possible to starve a tumor and stop its growth with a newly discovered small compound that blocks uptake of the vital ...

These foods may up your odds for colon cancer

January 18, 2018
(HealthDay)—Chowing down on red meat, white bread and sugar-laden drinks might increase your long-term risk of colon cancer, a new study suggests.

The pill lowers ovarian cancer risk, even for smokers

January 18, 2018
(HealthDay)—It's known that use of the birth control pill is tied to lower odds for ovarian cancer, but new research shows the benefit extends to smokers or women who are obese.

Modular gene enhancer promotes leukemia and regulates effectiveness of chemotherapy

January 18, 2018
Every day, billions of new blood cells are generated in the bone marrow. The gene Myc is known to play an important role in this process, and is also known to play a role in cancer. Scientists from the German Cancer Research ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.