Navigation Links
Novel drug therapy targets aggressive form of non-Hodgkin's lymphoma
Date:12/10/2012

NEW YORK (Dec. 10, 2012) -- Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin's lymphoma and the seventh most frequently diagnosed cancer. The most chemotherapy resistant form of DLBCL, called activated B-cell DLBCL (ABC-DLBCL), remains a major therapeutic challenge. An international research team, led by two laboratories from Weill Cornell Medical College, has developed a new experimental drug therapy to target this aggressive form of lymphoma.

In the journal Cancer Cell, researchers report the discovery of an experimental small molecule agent, MI-2, that irreversibly inactivates MALT1 -- a key protein responsible for driving the growth and survival of ABC-DLBCL cells.

"In our study we show the drug MI-2 we developed inactivates any MALT1 protein it touches, and without any apparent toxicity in animal models," says the study's lead investigator, Dr. Ari Melnick, associate professor of medicine and director of the Raymond and Beverly Sackler Center for Biomedical and Physical Sciences at Weill Cornell Medical College.

The research team, which includes investigators from Spain, Canada and several other U.S. institutions, are now working to optimize the drug while testing MI-2 with other drug therapies that could be less toxic than current chemotherapy regimens.

"No single drug can cure lymphoma. This is why we need to combine agents that can strike-out the different cellular pathways that lymphoma cells use to survive," says Dr. Melnick, who is also a hematologist-oncologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center. "We want to eliminate the use of toxic chemotherapy in the treatment of lymphoma patients, and these new study findings take us one-step closer to our goal of creating effective combinational molecular targeted therapy regimens to reduce treatment toxicity and improve lymphoma patient outcomes."

"A Bona Fide Therapeutic Target"

MALT1 is highly active in ABC-DLBCL and plays an important role in lymphoma cancer cell growth and survival. The unique protein is the only paracaspase produced in humans --and is a particular type of protease protein that cuts apart other proteins. But when MALT1 slices proteins in ABC-DLBCLs, it activates growth-promoting molecules and stops the work of other proteins that inhibit that growth.

"In essence, MALT1 turns off the brakes and presses the gas pedal to accelerate cell growth and survival in this aggressive cancer," Dr. Melnick says.

In this study, the researchers developed an activated form of MALT1 in the test tube that allowed them to study the structure of the molecule, and search for small molecule agents to shut it down. The key insights enabling this technical feat were achieved by co-lead investigator Dr. Hao Wu, an expert in biochemistry and structural biology and a former faculty member at Weill Cornell who is now at Harvard Medical School.

The researchers screened libraries of chemicals until they found one that tightly bonded to MALT1, preventing it from cutting other proteins. The agent, MI-2, also inactivated MALT1 in human samples of ABC-DLBCL, according to researchers.

When they tested the agent in mice, the research team found it stopped cancer growth without toxicity in normal tissues -- a trait Dr. Melnick says is due to the fact that MALT1 is not required for biological processes essential for life.

If tested successfully in human clinical trials, MI-2 could have benefits for other diseases, including MALT1 lymphoma, a lower-grade type of lymphoma. It could also possibly play a role in a variety of inflammatory and autoimmune disorders.

"MALT1 is a bona fide therapeutic target, and with the discovery of MI-2 we have provided a lead compound that forms the basis of a new class of therapeutic agents," says Dr. Melnick.

The Cornell Center for Technology Enterprise and Commercialization, on behalf of Cornell University, has filed a patent application on this research work.


'/>"/>

Contact: Lauren Woods
Law2014@med.cornell.edu
646-317-7401
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related medicine news :

1. Novel therapeutic agents provide hope for patients with hard-to-treat blood disorders
2. Researchers develop novel 3-D culture system for inflammatory breast cancer
3. ACNP: Novel NMDA receptor modulator significantly reduces depression scores within hours
4. Scripps Florida scientists uncover a novel cooperative effort to stop cancer spread
5. Novel mechanism through which normal stromal cells become cancer-promoting cells identified
6. Novel breast screening technology increases diagnostic accuracy
7. UNC, Vanderbilt discover a new live vaccine approach for SARS and novel coronaviruses
8. Moffitt Cancer Center researchers identify novel metabolic programs driving aggressive brain tumors
9. Novel treatment strategies for epilepsy
10. Taiho Pharmaceutical unveils data on 8 novel anticancer compounds
11. Researchers ID potential patient population who may benefit from novel anti-platelet treatment
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/29/2017)... ... 2017 , ... Patients interested in receiving quick and effective ... Cameron, with or without a referral. The FASTBRACES system is valued for its ... patient’s case, treatment with the FASTBRACES system could be completed in 120 days ...
(Date:3/29/2017)... ANN ARBOR, Mich. (PRWEB) , ... ... ... Global Retailer and Manufacturer Alliance (GRMA) is growing as it continues developing ... the dietary supplement industry. The organization, which plans to publish the first ...
(Date:3/29/2017)... ... March 29, 2017 , ... Altima Technologies, Inc., ... network and data center assets and audio-video devices has recently updated its Visio ... shapes for free and download shapes and stencils from http://www.VisioStencils.com. , ...
(Date:3/29/2017)... ... March 29, 2017 , ... ... oral braces. "The rubber bands used in conjunction with my braces always rubbed ... to design a way to prevent this problem." The O.B.S. was the result ...
(Date:3/29/2017)... ... March 29, 2017 , ... The assembly ... assembly protocols involve many repetitive steps and often scientists require many different versions ... high-throughput needed, and results in a lower error rate and cost saving for ...
Breaking Medicine News(10 mins):
(Date:3/29/2017)... , March 29, 2017  Novartis announced today ... has accepted the company,s Biologics License Application (BLA) ... an investigational chimeric antigen receptor T cell (CAR-T) ... young adult patients with B-cell acute lymphoblastic leukemia ... Novartis for a CAR-T. The priority review designation ...
(Date:3/29/2017)... Research and Markets has announced the addition of the "South ... & Forecast" report to their offering. ... The South Korean Proton Therapy Market is expected to ... Untapped Proton Therapy Market for South Korea was ... Proton Therapy plays an important role in delivering comprehensive cancer care to ...
(Date:3/29/2017)... 29, 2017  Zynex (OTCQB: ZYXI), an innovative medical technology ... medical devices for pain management, stroke rehabilitation, cardiac monitoring ... the Company,s 2016 full-year investor webcast on Monday, April 3, ... The Company expects to file its 2016 full year ... ...
Breaking Medicine Technology: