Navigation Links
Experimental drug combination selectively destroys lymphoma cells
Date:2/6/2013

Laboratory experiments conducted by scientists at Virginia Commonwealth University Massey Cancer Center suggest that a novel combination of the drugs ibrutinib and bortezomib could potentially be an effective new therapy for several forms of blood cancer, including diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

The study, published in the British Journal of Hematology, showed that the experimental drug combination killed cancer cells through a form of cell suicide known as apoptosis, but was relatively non-toxic to normal, healthy cells. Ibrutinib is a new agent that inhibits the B-cell receptor (BCR) signaling complex, which plays an important role in the survival of malignant B-cells. It has shown very promising initial results in the treatment of patients with B-cell malignancies, including chronic lymphocytic leukemia (CLL), DLBCL and MCL. The synergistic interaction of the two drugs proved lethal even to lymphoma cells that had become resistant to bortezomib, when used alone.

"Bortezomib is currently used to treat MCL and multiple myeloma, but, unfortunately, many patients develop resistance to the drug," says the study's principle investigator 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. "We are hopeful that this combination therapy may circumvent such resistance and eventually help fill an urgent need for more effective therapies for patients with these uncommon blood disorders."

With cultured DLBCL and MCL cells in laboratory experiments spearheaded by Girija Dasmahapatra, Ph.D., lead author of the study's manuscript and instructor in the Department of Internal Medicine at VCU School of Medicine, the scientists found that ibrutinib blocked several molecular pathways that the cancer cells use for growth and survival. When ibrutinib was combined with bortezomib, the scientists observed a high level of synergism between the two drugs that resulted in profound cell death due to DNA damage, culminating in apoptosis. The research findings suggest that the effectiveness of the combination therapy against bortezomib-resistant lymphoma cells may stem from ibrutinib's ability to block signaling pathways used by the cancer cells to survive bortezomib exposure.

Specifically, exposure of DLBCL and MCL cells to ibrutinib blocked the cancer-promoting NF-κB, AKT and ERK1/2 signaling pathways. These signaling pathways provide cells with the ability to adapt to otherwise harmful environmental stimuli by transmitting messages from receptors located at the cell's surface to proteins within the cell that trigger a variety of biological processes. In particular, NF-κB, AKT and ERK1/2 have been shown to carry out many functions that allow cancer cells to survive and proliferate. Significantly, each of these pathways has been implicated in the development of resistance to proteasome inhibitors such as bortezomib.

"We have provided a framework for understanding how an agent like ibrutinib might be employed to enhance the activity of an established anti-cancer agent like bortezomib," says Grant. "We are currently working with representatives from the pharmaceutical industry and the National Cancer Institute to develop a new treatment strategy in which ibrutinib will be combined with proteasome inhibitors like bortezomib for the treatment of patients with lymphomas and potentially other blood cancers."


'/>"/>

Contact: John Wallace
wallacej@vcu.edu
804-628-1550
Virginia Commonwealth University
Source:Eurekalert  

Related biology news :

1. Nicole George wins 2012 Journal of Experimental Biology Outstanding Paper Prize
2. FASEB SRC announces conference registration open for: Genetic Recombination & Genome Rearrangements
3. TGen, Scottsdale Healthcare study shows drug combination extends pancreatic cancer patient survival
4. Cats are able to navigate complex combinations of wet and dry foods to achieve a consistent intake of protein, fat and carbohydrate
5. Combination of two pharmaceuticals proves effective in the treatment of multiple sclerosis
6. Hormone combination effective and safe for treating obesity in mice
7. Insecticide resistance caused by recombination of 2 genes
8. New line of approach for combination therapy against melanoma
9. New study finds a protein combination is best to consume post-workout for building muscle
10. Research breakthrough selectively represses the immune system
11. New way to kill lymphoma without chemotherapy
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Experimental drug combination selectively destroys lymphoma cells
(Date:12/8/2016)... Calif. , Dec. 8, 2016  Singulex, Inc., ... Molecule Counting technology, entered into a license and supply ... serving science. The agreement provides Singulex access to Thermo ... Europe is used to diagnose systemic ... United States to aid in assessing the ...
(Date:12/7/2016)...   Veridium , a leader in biometrics-based ... CEO James Stickland . Stickland, a seasoned ... has served in senior executive roles for HSBC, ... expanding a pipeline of venture capital and accelerating ... served as managing director of U.K.-based fintech firm ...
(Date:12/5/2016)... , Dec. 5, 2016  The Office of ... published "Can CT Scans Enhance or Replace Medico ... potential of supporting or replacing forensic autopsies with ... scan. In response to recommendations made ... exploring using CT scans as a potential component ...
Breaking Biology News(10 mins):
(Date:12/8/2016)... Eurofins announces the appointment of Sean Murray , National Division ... Mr. Murray will bring valuable expertise to the ... leading international business teams. As the National Division Leader, he will ... status as the global leader in bio-analytical testing services. ... , , ...
(Date:12/8/2016)... Dec. 8, 2016  Anaconda BioMed S.L., a pre-clinical ... the next generation neuro-thrombectomy system for the treatment of ... G. Jovin, MD to join its Scientific Advisory Board ... strategic network of scientific and clinical experts to Anaconda ... the ANCD BRAIN ® to its clinical phase. ...
(Date:12/8/2016)... 8, 2016  Soligenix, Inc. (OTCQB: SNGX) (Soligenix ... on developing and commercializing products to treat rare ... announced today the long-term follow-up data from its ... first-in-class Innate Defense Regulator (IDR), in the treatment ... cancer patients undergoing chemoradiation therapy (CRT).  The additional ...
(Date:12/8/2016)... -- Partnering to fuel Philadelphia,s innovative ... Southeastern Pennsylvania (" Ben Franklin "); ... Blue Cross; and Safeguard Scientifics ("Safeguard") (NYSE: ... million funding initiative over a four year period to ... a burgeoning economic vitality in digital health, Ben ...
Breaking Biology Technology: