Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team validates potentially powerful new way to treat HER2-positive breast cancer

19.05.2014

Scientists at Cold Spring Harbor Laboratory (CSHL) today report a discovery that they hope will lead to the development of a powerful new way of treating an aggressive form of breast cancer.

The breast cancer subtype in question is commonly called "HER2-positive"; it's a subset of the disease affecting about one patient in four, in which tumor cells overexpress a signaling protein called HER2.

The blockbuster drug Herceptin is a treatment of choice for many women with HER2-positive breast cancer, but in most cases, resistance to the treatment develops within several years. The prognosis for HER2-positive breast cancer patients is worse than for those with other subtypes of the illness.

In a paper appearing online today in Nature Chemical Biology, a multi-institution team led by CSHL Professor Nicholas Tonks reports that it has found a means of inhibiting another protein, called PTP1B, whose expression is also upregulated in HER2-positive breast cancer. PTP1B has been shown to play a critical role in the development of tumors in which HER2 signaling is aberrant.

... more about:
»Biology »CSHL »Cold »HER2 »HER2-positive »Harbor »PTP1B »breast »phosphate »proteins

When they treated mice modeling HER2-positive breast cancer with a PTP1B inhibitor called MSI-1436 (also called trodusquemine), Tonks and colleagues inhibited signaling by HER2 proteins.

"The result was an extensive inhibition of tumor growth and prevention of metastasis to the lung in HER2-positive animal models of breast cancer," notes Navasona Krishnan, Ph.D., a postdoctoral investigator in the Tonks lab who performed many of the experiments and is lead author on the paper reporting the results.

Dr. Tonks discovered PTP1B some 25 years ago. It is an enzyme – one in a "superfamily" of 105 called protein tyrosine phosphatases (PTPs) -- that perform the essential biochemical task of removing phosphate groups from amino acids called tyrosines in other proteins. Adding and removing phosphate groups is one of the means by which signals are sent among proteins.

PTP1B for many years has been a target of interest among drug developers. It is well known to be a negative regulator of insulin – an antagonist of insulin signaling -- and of signaling by leptin, the hormone that helps regulate appetite. Drugs that can block or inhibit the action of PTP1B have great potential in controlling diabetes and obesity. Yet properties of the molecule -- involving both its charged active binding site and its shape – have stymied potential developers of inhibitory drugs.

The new paper by Tonks and collaborators importantly reveals an alternative binding site, called an allosteric site, that does not present the biochemical difficulties that the active, or "catalytic," binding site does. This allosteric site is a target of the candidate drug trodusquemine.

Later this year early-stage human trials will begin for the drug, a collaboration of CSHL and North Shore-Long Island Jewish Hospital. Dr. Tonks and CSHL have interests in a joint venture called DepYmed Inc., in partnership with Ohr Pharmaceutical (NasdaqCM: OHRP). The venture seeks to develop trodusquemine and related analogs.

###

Funders for the research discussed in this release include: the National Institutes of Health, Cold Spring Harbor Laboratory Cancer Center, American Diabetes Association, Brown University Research Seed Fund, and Agence Nationale de Researche.

"Targeting the disordered C terminus of PTP1B with an allosteric inhibitor" appears online ahead of print Sunday, May 18, 2014 in Nature Chemical Biology. The authors are: Navasona Krishnan, Dorothy Koveal, Daniel H. Miller, Bin Xue, Sai Dipikaa Akshinthala, Jaka Kragelj, Malene Ringkjobing Jensen, Carla-Maria Gauss, Rebecca Page, Martin Blackledge, Senthil K. Musthuswamy, Wolfgang Peti and Nicholas K. Tonks. the paper can be obtained at: http://www.nature.com/nchembio/journal/vaop/ncurrent/index.html

About Cold Spring Harbor Laboratory

Founded in 1890, Cold Spring Harbor Laboratory (CSHL) has shaped contemporary biomedical research and education with programs in cancer, neuroscience, plant biology and quantitative biology. CSHL is ranked number one in the world by Thomson Reuters for the impact of its research in molecular biology and genetics. The Laboratory has been home to eight Nobel Prize winners. Today, CSHL's multidisciplinary scientific community is more than 600 researchers and technicians strong and its Meetings & Courses program hosts more than 12,000 scientists from around the world each year to its Long Island campus and its China center. For more information, visit http://www.cshl.edu.

Peter Tarr | Eurek Alert!

Further reports about: Biology CSHL Cold HER2 HER2-positive Harbor PTP1B breast phosphate proteins

More articles from Health and Medicine:

nachricht New evidence: How amino acid cysteine combats Huntington's disease
27.07.2016 | Johns Hopkins Medicine

nachricht Cord blood outperforms matched, unrelated donor in bone marrow transplant
27.07.2016 | University of Colorado Anschutz Medical Campus

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Self-assembling nano inks form conductive and transparent grids during imprint

Transparent electronics devices are present in today’s thin film displays, solar cells, and touchscreens. The future will bring flexible versions of such devices. Their production requires printable materials that are transparent and remain highly conductive even when deformed. Researchers at INM – Leibniz Institute for New Materials have combined a new self-assembling nano ink with an imprint process to create flexible conductive grids with a resolution below one micrometer.

To print the grids, an ink of gold nanowires is applied to a substrate. A structured stamp is pressed on the substrate and forces the ink into a pattern. “The...

Im Focus: The Glowing Brain

A new Fraunhofer MEVIS method conveys medical interrelationships quickly and intuitively with innovative visualization technology

On the monitor, a brain spins slowly and can be examined from every angle. Suddenly, some sections start glowing, first on the side and then the entire back of...

Im Focus: Newly discovered material property may lead to high temp superconductivity

Researchers at the U.S. Department of Energy's (DOE) Ames Laboratory have discovered an unusual property of purple bronze that may point to new ways to achieve high temperature superconductivity.

While studying purple bronze, a molybdenum oxide, researchers discovered an unconventional charge density wave on its surface.

Im Focus: Mapping electromagnetic waveforms

Munich Physicists have developed a novel electron microscope that can visualize electromagnetic fields oscillating at frequencies of billions of cycles per second.

Temporally varying electromagnetic fields are the driving force behind the whole of electronics. Their polarities can change at mind-bogglingly fast rates, and...

Im Focus: Continental tug-of-war - until the rope snaps

Breakup of continents with two speed: Continents initially stretch very slowly along the future splitting zone, but then move apart very quickly before the onset of rupture. The final speed can be up to 20 times faster than in the first, slow extension phase.phases

Present-day continents were shaped hundreds of millions of years ago as the supercontinent Pangaea broke apart. Derived from Pangaea’s main fragments Gondwana...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

GROWING IN CITIES - Interdisciplinary Perspectives on Urban Gardening

15.07.2016 | Event News

SIGGRAPH2016 Computer Graphics Interactive Techniques, 24-28 July, Anaheim, California

15.07.2016 | Event News

Partner countries of FAIR accelerator meet in Darmstadt and approve developments

11.07.2016 | Event News

 
Latest News

World first demo of labyrinth magnetic-domain-optical Q-switched laser

28.07.2016 | Information Technology

New material could advance superconductivity

28.07.2016 | Materials Sciences

CO2 can be stored underground for 10 times the length needed to avoid climatic impact

28.07.2016 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>