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 Amputees can learn to control a robotic arm with their minds
28.11.2017 | University of Chicago Medical Center

nachricht The importance of biodiversity in forests could increase due to climate change
17.11.2017 | Deutsches Zentrum für integrative Biodiversitätsforschung (iDiv) Halle-Jena-Leipzig

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: Long-lived storage of a photonic qubit for worldwide teleportation

MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.

Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...

Im Focus: Electromagnetic water cloak eliminates drag and wake

Detailed calculations show water cloaks are feasible with today's technology

Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...

Im Focus: Scientists channel graphene to understand filtration and ion transport into cells

Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.

To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...

Im Focus: Towards data storage at the single molecule level

The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.

Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...

Im Focus: Successful Mechanical Testing of Nanowires

With innovative experiments, researchers at the Helmholtz-Zentrums Geesthacht and the Technical University Hamburg unravel why tiny metallic structures are extremely strong

Light-weight and simultaneously strong – porous metallic nanomaterials promise interesting applications as, for instance, for future aeroplanes with enhanced...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

AKL’18: The opportunities and challenges of digitalization in the laser industry

07.12.2017 | Event News

 
Latest News

Long-lived storage of a photonic qubit for worldwide teleportation

12.12.2017 | Physics and Astronomy

Multi-year submarine-canyon study challenges textbook theories about turbidity currents

12.12.2017 | Earth Sciences

Electromagnetic water cloak eliminates drag and wake

12.12.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>