Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New subtype of breast cancer responds to targeted drug

02.03.2010
A newly identified cancer biomarker could define a new subtype of breast cancer as well as offer a potential way to treat it, say researchers at Washington University School of Medicine in St. Louis. Their findings will be published in the March 1 online early edition issue of the Proceedings of the National Academy of Sciences.

The research could further refine what recent breast cancer research has concluded: that breast cancer is not one disease, but many. So far, research has firmly established that at least five subtypes of breast cancer exist, each having distinct biological features, clinical outcomes and responses to traditional therapies.

The biomarker identified by the Washington University researchers is found frequently in breast cancers and especially in those that have poorer outcomes. It stems from overactivation of a gene called LRP6 (low-density lipoprotein receptor-related protein 6), which stimulates an important cell-growth signaling pathway. LRP6 can be inhibited by a protein discovered in the same laboratory, which could become an effective drug against the breast cancer type, the researchers say.

"We found increased expression of the LRP6 gene in about a quarter of breast cancer specimens we examined, and we think LRP6 overexpression could be a marker for a new class of breast cancer," says Guojun Bu, Ph.D., professor of pediatrics and of cell biology and physiology. "In addition, we found that this biomarker is often associated with breast cancers that are either harder to treat or more likely to recur. We already have an agent that seems to be effective against LRP6-overexpressing tumors, which could someday become a therapy for tumors that right now have few treatment options."

The research was conducted primarily by Chia-Chen Liu, a graduate student in the Bu lab, who is a fellow in the Cancer Biology Pathway Program at the Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital.

The researchers' analysis of human breast cancer tissue samples found significant increases in LRP6 levels in 20 percent to 36 percent of the tumors. LRP6 was increased more frequently in ER (estrogen receptor)-negative or HER2 (human epidermal growth factor receptor 2)-negative samples. LRP6 was also increased more frequently in so-called triple-negative breast tumor samples, which test negative for ER, HER2 and PR (progesterone receptor).

In general, patients who have triple-negative breast cancers have an increased risk of disease recurrence after initial treatment and a poorer prognosis. Furthermore, although ER-positive and HER2-positive tumors can be targeted with specific therapies, ER-negative and HER2-negative tumors cannot. So it appears that LRP6 overexpression is often associated with tumors that are currently difficult to treat, says Bu.

Research in the lab had earlier discovered a protein that binds to and inhibits LRP6. This study showed that the protein, called Mesd (mesoderm development), was able to slow the growth of breast cancer cells in the laboratory and to inhibit mammary tumor growth in laboratory mice.

Importantly, mice treated with Mesd did not experience any of the known side effects, such as bone lesions, skin disorders or intestinal malfunctions, associated with inhibition of this growth pathway.

"Our work introduces Mesd as a promising antitumor agent that might be further developed for breast cancer therapy," Bu says. "It would be analogous to such successful breast cancer therapies as Herceptin (trastuzumab), which specifically targets HER2-positive breast cancer."

The researchers also found that a small segment of Mesd has the same effect as the larger molecule. This segment, or peptide, is more stable than the whole protein molecule and can be easily synthesized.

The researchers have patented the protein and the peptide through the university's Office of Technology Management. Recently, Raptor Pharmaceutical Corp. licensed Mesd from the university to develop it for clinical use.

Liu C-C, Prior J, Piwnica-Worms D, Bu G. LRP6 overexpression defines a class of breast cancer subtype and is a target for therapy. Proceedings of the National Academy of Sciences. March 1, 2010 (advance online publication).

Funding from the National Institutes of Health and the Siteman Cancer Center supported this research.

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Siteman Cancer Center is the only federally designated Comprehensive Cancer Center within a 240-mile radius of St. Louis. Siteman Cancer Center is composed of the combined cancer research and treatment programs of Barnes-Jewish Hospital and Washington University School of Medicine. Siteman has satellite locations in West County and St. Peters, in addition to its full-service facility at Washington University Medical Center on South Kingshighway.

Gwen Ericson | EurekAlert!
Further information:
http://www.wustl.edu

Further reports about: Barnes-Jewish Cancer HER2 HER2-positive LRP6 Medicine Science TV breast cancer cancer research

More articles from Health and Medicine:

nachricht GLUT5 fluorescent probe fingerprints cancer cells
20.04.2018 | Michigan Technological University

nachricht Scientists re-create brain neurons to study obesity and personalize treatment
20.04.2018 | Cedars-Sinai Medical Center

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: Molecules Brilliantly Illuminated

Physicists at the Laboratory for Attosecond Physics, which is jointly run by Ludwig-Maximilians-Universität and the Max Planck Institute of Quantum Optics, have developed a high-power laser system that generates ultrashort pulses of light covering a large share of the mid-infrared spectrum. The researchers envisage a wide range of applications for the technology – in the early diagnosis of cancer, for instance.

Molecules are the building blocks of life. Like all other organisms, we are made of them. They control our biorhythm, and they can also reflect our state of...

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
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

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Structured light and nanomaterials open new ways to tailor light at the nanoscale

23.04.2018 | Physics and Astronomy

On the shape of the 'petal' for the dissipation curve

23.04.2018 | Physics and Astronomy

Clean and Efficient – Fraunhofer ISE Presents Hydrogen Technologies at the HANNOVER MESSE 2018

23.04.2018 | Trade Fair News

VideoLinks
Science & Research
Overview of more VideoLinks >>>