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 On track to heal leukaemia
18.01.2017 | Universitätsspital Bern

nachricht Penn vet research identifies new target for taming Ebola
12.01.2017 | University of Pennsylvania

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: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>