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

lls 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."


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

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Experimental drug combination selectively destroys lymphoma cells
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