Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Molecule common in some cancers, rheumatoid arthritis leads to potential therapy for both

14.11.2013
A molecule that helps cells stick together is significantly over-produced in two very different diseases — rheumatoid arthritis and a variety of cancers, including breast and brain tumors, concludes a new study. The scientists who made the discovery also found candidate drugs to inhibit the molecule, cadherin-11, one of which is already in a clinical trial.

The study, published in Oncotarget, was led by investigators at Georgetown University Medical Center, and included collaborators from Harvard and Columbia Universities, Mayo Clinic and Queen's University in Belfast, Northern Ireland.

"Our findings suggest that cadherin-11 is important for cancer progression as well as rheumatoid arthritis — for reasons we do not fully understand. Nevertheless, we are rapidly translating this discovery for use in the clinic," says the study's senior investigator, Stephen Byers, PhD, a professor and molecular oncologist at Georgetown Lombardi Comprehensive Cancer Center.

Byers and his Georgetown colleagues, Shahin Assefnia DVM, Siva Dakshanurthy PhD, and Jaime Guidry Auvil, PhD, have found that cadherin-11 is over-expressed in 15 percent of breast cancers, and in many glioblastomas. He believes the molecule also contributes to pancreatic cancer.

"What most of these cancers all have in common is cadherin-11 and a poor prognosis, with no effective therapies," Byers says. "Cadherin-11 expression is required for tumors to grow. If it is blocked, the cancers in cell line studies and in animals just stop growing — which is really quite striking."

The Georgetown team has developed a small molecule agent to shut down cadherin-11 in cancer, and, by screening drugs now on the market, found that the well known arthritis drug Celebrex acts in a similar way. While it is unlikely that Celebrex could be used as a single agent against cancer because it would be too toxic at the level needed to impair cadherin-11, a Celebrex-related molecule works the same way, and may potentially be less toxic.

Co-author Michael Brenner, MD, at Harvard University, has designed an antibody that can shut down cadherin-11 in rheumatoid arthritis. The Oncotarget study demonstrated that Brenner's antibody worked in animal models of tumors that made cadherin-11.

It was chance that he and Brenner were working on the same molecule at the same time and came to know of each other's work. Coincidentally, co-author Lawrence Shapiro, PhD, at Columbia, was building a crystal structure of cadherin-11 and is now working with Byers and Brenner to show how the molecule binds to Celebrex and other small molecule drug cadherin-11 inhibitors.

This close collaboration led Byers, Brenner and Shapiro to apply for a grant last year from the National Cancer Institute's Provocative Questions project. They proposed answering the question related to the connection between drugs, such as anti-inflammatory agents, that can protect against cancer and other conditions.

The trio won the $2.5 million grant (R01 CA170653) for that question — and some of the findings fueled by that grant are included in this study.

This research also was funded by awards from the Department of Defense's Breast Cancer Research Program (W81XWH-10-1-0437 and DOD BC62416).

Byers, Dakshanamurthy, Auvil and co-author Milton Brown, MD, PhD are inventors on patent applications that have been filed by Georgetown University on technologies that are related to this project. Brenner is founder of Adheron Therapeutics, which has developed best in class cadherin-11 antibodies for therapeutic use in rheumatoid arthritis and cancer.

About Georgetown Lombardi Comprehensive Cancer Center

Georgetown Lombardi Comprehensive Cancer Center, part of Georgetown University Medical Center and MedStar Georgetown University Hospital, seeks to improve the diagnosis, treatment, and prevention of cancer through innovative basic and clinical research, patient care, community education and outreach, and the training of cancer specialists of the future. Georgetown Lombardi is one of only 41 comprehensive cancer centers in the nation, as designated by the National Cancer Institute (grant #P30 CA051008), and the only one in the Washington, DC area. For more information, go to http://lombardi.georgetown.edu.

About Georgetown University Medical Center

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through MedStar Health). GUMC's mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis – or "care of the whole person." The Medical Center includes the School of Medicine and the School of Nursing & Health Studies, both nationally ranked; Georgetown Lombardi Comprehensive Cancer Center, designated as a comprehensive cancer center by the National Cancer Institute; and the Biomedical Graduate Research Organization (BGRO), which accounts for the majority of externally funded research at GUMC including a Clinical and Translational Science Award from the National Institutes of Health.

Karen Mallet | EurekAlert!
Further information:
http://www.georgetown.edu

More articles from Health and Medicine:

nachricht Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena

nachricht Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University

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: First-of-its-kind chemical oscillator offers new level of molecular control

DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.

Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...

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...

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

Engineers program tiny robots to move, think like insects

15.12.2017 | Power and Electrical Engineering

One in 5 materials chemistry papers may be wrong, study suggests

15.12.2017 | Materials Sciences

New antbird species discovered in Peru by LSU ornithologists

15.12.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>