Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

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

19.05.2010
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:
http://www.umich.edu

More articles from Studies and Analyses:

nachricht WAKE-UP provides new treatment option for stroke patients | International study led by UKE
17.05.2018 | Universitätsklinikum Hamburg-Eppendorf

nachricht First form of therapy for childhood dementia CLN2 developed
25.04.2018 | Universitätsklinikum Hamburg-Eppendorf

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: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>