Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New drug combination therapy developed to treat leukemia

18.04.2013
A new, pre-clinical study by researchers at Virginia Commonwealth University Massey Cancer Center suggests that a novel drug combination could lead to profound leukemia cell death by disrupting the function of two major pro-survival proteins. The effectiveness of the therapy lies in its ability to target a pro-survival cell signaling pathway known as PI3K/AKT/mTOR, upon which the leukemia cells have become dependent.

In the study, published in the journal Cancer Research, researchers combined the drug ABT-737 with another agent BEZ235. ABT-737 targets proteins known as B-cell lymphoma 2 (Bcl-2) and Bcl-xL, which prevent apoptosis, a form of cell suicide, in cancer cells. BEZ235 directly inhibits the PI3K/AKT/mTOR pathway, and as a result, reduces the expression of another anti-apoptotic protein known as Mcl-1, which is not targeted by ABT-737. Among their many functions, signaling pathways regulate biological processes required for cellular survival. The PI3K/AKT/mTOR pathway helps keep apoptosis in check, in part, by controlling the production of Mcl-1.

However, the pathway can become dysregulated in cancer, and in so doing, contribute to uncontrolled tumor growth and resistance to conventional cancer therapies. It is activated in 50 to 80 percent of patients with acute myelogenous leukemia (AML), and in some, but not all cases, is associated with genetic mutations. Significantly, disabling both anti-apoptotic proteins, Bcl-2 and Bcl-xL, in conjunction with Mcl-1, caused profound cell death of leukemia cells in the test tube as well as in animal models of AML.

"This study builds on many years of work in our laboratory investigating the mechanisms that regulate apoptosis in human leukemia cells. To the best of our knowledge, it is the first to raise the possibility that activation of the P13K/AKT/mTOR pathway, rather than genetic mutations within the pathway, may represent the best predictor of leukemia cell responses to these targeted agents," says one of the study's key researchers Steven Grant, M.D., Shirley Carter Olsson and Sture Gordon Olsson Chair in Oncology Research, associate director for translational research, program co-leader of Developmental Therapeutics and Cancer Cell Signaling research member at VCU Massey Cancer Center. "These findings could lead to a new therapeutic strategy for patients with AML and potentially other diseases by targeting patients whose leukemia cells display activation of a specific survival pathway."

Grant's team made another discovery that helped explain the new therapy's effectiveness. They found that the therapy releases and/or activates the pro-apoptotic proteins Bim, Bak and Bax, which help trigger apoptosis. Thus, in addition to disabling major pro-survival proteins, the combination therapy also helps to unleash several additional proteins that promote apoptosis.

Moving forward, Grant and his team hope to work with pharmaceutical companies and the National Cancer Institute to develop strategies combining inhibitors of the PI3K/AKT/mTOR pathway with Bcl-2 family antagonists for the treatment of patients with AML.

Grant collaborated on this research with lead author Mohamed Rahmani, Ph.D., associate professor of internal medicine at the VCU School of Medicine, who spearheaded this research. Other collaborators included David C. Williams M.D., Ph.D., co-director of the Tissue and Data Acquisition and Analysis Core at VCU Massey Cancer Center, researcher in the Developmental Therapeutics program at Massey and assistant professor in the VCU Department of Pathology; and Andrea Ferreira-Gonzalez, Ph.D., professor in the VCU Department of Pathology.

This research was supported by National Institutes of Health grants CA93738, CA100866-01, CA130805, CA142509, and CA148431; awards from the Leukemia and Lymphoma Society of America and the Multiple Myeloma Research Foundation; and, in part, by funding from VCU Massey Cancer Center's NIH-NCI Cancer Center Support Grant P30 CA016059.

The full manuscript of this study can be found online at: http://cancerres.aacrjournals.org/content/73/4/1340.long.

News directors: Broadcast access to VCU Massey Cancer Center experts is available through VideoLink ReadyCam. ReadyCam transmits video and audio via fiber optics through a system that is routed to your newsroom. To schedule a live or taped interview, contact Alaina Farrish, (804) 628-4578.

About VCU Massey Cancer Center

VCU Massey Cancer Center is one of only 67 National Cancer Institute-designated institutions in the country that leads and shapes America's cancer research efforts. Working with all kinds of cancers, the Center conducts basic, translational and clinical cancer research, provides state-of-the-art treatments and clinical trials, and promotes cancer prevention and education. Since 1974, Massey has served as an internationally recognized center of excellence. It has one of the largest offerings of clinical trials in Virginia and serves patients in Richmond and in four satellite locations. Its 1,000 researchers, clinicians and staff members are dedicated to improving the quality of human life by developing and delivering effective means to prevent, control and ultimately to cure cancer. Visit Massey online at http://www.massey.vcu.edu or call 877-4-MASSEY for more information.

About VCU and the VCU Medical Center

Virginia Commonwealth University is a major, urban public research university with national and international rankings in sponsored research. Located in downtown Richmond, VCU enrolls more than 31,000 students in 222 degree and certificate programs in the arts, sciences and humanities. Sixty-six of the programs are unique in Virginia, many of them crossing the disciplines of VCU's 13 schools and one college. MCV Hospitals and the health sciences schools of Virginia Commonwealth University compose the VCU Medical Center, one of the nation's leading academic medical centers. For more, see http://www.vcu.edu.

Alaina Farrish | EurekAlert!
Further information:
http://www.vcu.edu

More articles from Health and Medicine:

nachricht Organ-on-a-chip mimics heart's biomechanical properties
23.02.2017 | Vanderbilt University

nachricht Researchers identify cause of hereditary skeletal muscle disorder
22.02.2017 | Klinikum der Universität München

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: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Stingless bees have their nests protected by soldiers

24.02.2017 | Life Sciences

New risk factors for anxiety disorders

24.02.2017 | Life Sciences

MWC 2017: 5G Capital Berlin

24.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>