Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Gene fusions may be the ‘smoking gun’ in prostate cancer development

Drugs should be developed to target gene fusions in prostate cancer, research shows
Prostate cancer treatments that target the hormone androgen and its receptor may be going after the wrong source, according to a new study. Researchers have found that when two genes fuse together to cause prostate cancer, it blocks the receptor for the hormone androgen, preventing prostate cells from developing normally.

The study, from the University of Michigan Comprehensive Cancer Center, suggests that the gene fusion – not the androgen receptor – is a more specific “bad actor” in prostate cancer and is the real smoking gun that should be targeted by treatments.

“We need to begin to think about targeting prostate cancer by targeting the gene fusion, and not confining our approaches to androgen receptor. If we’re going to find a more durable therapy, we need to get at the gene fusion,” says study author Arul Chinnaiyan, M.D. Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Endowed Professor of Pathology at the U-M Medical School. Chinnaiyan is also a Howard Hughes Medical Institute investigator and an American Cancer Society research professor.

The study is featured on the cover of the May 18 issue of Cancer Cell.

Treatments for prostate cancer typically include drugs to moderate androgen, a male hormone that controls the normal growth of the prostate. These drugs typically work at first, but over time the cancer cells become resistant to the therapy and the cancer returns. Because it’s no longer responsive to currently available hormone deprivation therapies, the recurrent cancer is usually more difficult to treat.

In 2005, Chinnaiyan and his team identified a prostate-specific gene called TMPRSS2 that fuses with a cancer-causing gene called ERG. The team’s earlier research has shown that this gene fusion acts as an “on switch” to trigger prostate cancer.

This new study used sophisticated sequencing technologies to map the genome-wide location of androgen receptor and the TMPRSS2-ERG gene fusion in prostate cancer cells. The researchers found that the gene fusion blocks the androgen receptor directly and also interferes with it at the genetic level to prevent normal androgen receptor signaling. With the androgen receptor blocked, prostate cells stop growing and developing normally, allowing cancer to develop.

“Our study shows the underlying problem in prostate cancer is the presence of a gene fusion, not the androgen receptor. In many contexts, androgen signaling is actually a good thing, but the presence of the gene fusion blocks androgen receptor signaling, which alters normal prostate cell development. While current treatments for advanced prostate cancer are focused on hormone deprivation and are quite effective, at least initially, future therapies need to be developed that target the prostate cancer gene fusion,” Chinnaiyan says.

Prostate cancer statistics: 192,280 Americans will be diagnosed with prostate cancer this year and 27,360 will die from the disease, according to the American Cancer Society

Additional authors: Jindan Yu, Jianjun Yu, Ram-Shankar Mani, Qi Cao, Chad J. Brenner, Xuhong Cao, George X. Wang, Longtao Wu, James Li, Ming Hu, Yusong Gong, Hong Cheng, Bharathi Laxman, Adaikkalam Vellaichamy, Sunita Shankar, Yong Li, Saravana M. Dhanasekaran, Roger Morey, Terrence Barrette, Robert J. Lonigro, Scott A. Tomlins, Sooryanarayana Varambally and Zhaohui S. Qin

Funding: Prostate Cancer Foundation, Burroughs Wellcome Foundation, Doris Duke Charitable Foundation, Howard Hughes Medical Institute, American Cancer Society, U-M Prostate Specialized Program of Research Excellence, Early Detection Research Network, U.S. Department of Defense

Disclosure: The University of Michigan recently received a patent on the detection of gene fusions in prostate cancer (US 7,718,369), on which Tomlins and Chinnaiyan are co-inventors. The diagnostic field of use has been licensed to Gen-Probe Inc. Chinnaiyan also has a sponsored research agreement with Gen-Probe. Gen-Probe has had no role in the design or experimentation of this study, nor has it participated in the writing of the manuscript.

Reference: Cancer Cell, Vol. 17, No. 5, pp. 443-454

Nicole Fawcett | EurekAlert!
Further information:

More articles from Studies and Analyses:

nachricht Diagnoses: When Are Several Opinions Better Than One?
19.07.2016 | Max-Planck-Institut für Bildungsforschung

nachricht High in calories and low in nutrients when adolescents share pictures of food online
07.04.2016 | University of Gothenburg

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Novel mechanisms of action discovered for the skin cancer medication Imiquimod

21.10.2016 | Life Sciences

Second research flight into zero gravity

21.10.2016 | Life Sciences

How Does Friendly Fire Happen in the Pancreas?

21.10.2016 | Life Sciences

More VideoLinks >>>