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:4/13/2017)... April 13, 2017 According to a new market ... Identity Analytics, Identity Administration, and Authorization), Service, Authentication Type, Deployment Mode, Vertical, ... Market is expected to grow from USD 14.30 Billion in 2017 to ... of 17.3%. ... MarketsandMarkets Logo ...
(Date:4/11/2017)... 2017 No two people are believed ... New York University Tandon School of Engineering and ... that partial similarities between prints are common enough ... phones and other electronic devices can be more ... lies in the fact that fingerprint-based authentication systems ...
(Date:4/5/2017)... SEATTLE , April 5, 2017  The Allen ... the Allen Cell Explorer: a one-of-a-kind portal and dynamic ... large-scale 3D imaging data, the first application of deep ... edited human stem cell lines and a growing suite ... the platform for these and future publicly available resources ...
Breaking Biology News(10 mins):
(Date:10/11/2017)... Bay, Florida (PRWEB) , ... October 11, 2017 ... ... and Drug Administration (FDA) has granted orphan drug designation to SBT-100, its novel ... (sdAb) for the treatment of osteosarcoma. SBT-100 is able to cross the cell ...
(Date:10/10/2017)... ... October 10, 2017 , ... ... company advancing targeted antibody-drug conjugate (ADC) therapeutics, today confirmed licensing rights that ... Polymerized Liposomal Nanoparticle), a technology developed in collaboration with Children’s Hospital Los ...
(Date:10/10/2017)... Poway, California (PRWEB) , ... October 10, 2017 , ... ... afternoon speaking at his local San Diego Rotary Club. The event ... San Diego, CA and had 300+ attendees. Dr. Harman, DVM, MPVM was joined ...
(Date:10/10/2017)... Calif. , Oct. 10, 2017 SomaGenics ... from the NIH to develop RealSeq®-SC (Single Cell), expected ... for profiling small RNAs (including microRNAs) from single cells ... Program highlights the need to accelerate development of approaches ... "New techniques for measuring levels ...
Breaking Biology Technology: