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Scientists pinpoint protein that could improve small cell lung cancer therapies
Date:4/22/2014

Approximately 15 percent of all lung cancers are small cell lung cancers (SCLC), which grow rapidly and often develop resistance to chemotherapy. However, researchers at Virginia Commonwealth University Massey Cancer Center have revealed new insights into the mechanisms leading to this resistance that may lead to improved therapies.

Chemotherapies work primarily by mediating B-cell lymphoma 2 (Bcl-2) family proteins, which are responsible for regulating cell death. Depending on their function, this family of proteins can trigger a form of cell suicide known as apoptosis or they can activate mechanisms that prevent apoptosis and promote cell survival. Recently, drugs have been developed that block the function of pro-survival Bcl-2 family proteins. One of these drugs known as ABT-737, and its orally available derivative ABT-263 (currently being tested in clinical trials), has been shown to kill SCLC cells and potentially increase the effectiveness of chemotherapies that affect Bcl-2 family proteins. However, the effectiveness of ABT-737 varies greatly in a broad range of SCLC cells.

In a recent study published in Nature Publishing Group's journal Cell Death & Disease, Massey researchers Hisashi Harada, Ph.D., and Geoffrey Krystal, M.D., Ph.D., discovered that the expression of a protein called Noxa is critical to the effectiveness of ABT-737 because it helps regulate the function of MCL-1, another pro-survival Bcl-2 family protein. Through experiments with cultured SCLC cells, the researchers found that Noxa recruits MCL-1 to the mitochondria, the cell's power producer, which degrades MCL-1 and makes the cancer cells more sensitive to ABT-737.

"Essentially, we discovered how ABT-737 works and why some small cell lung cancer cells are not as affected by it," says Harada, member of the Cancer Cell Signaling research program at Massey and assistant professor in the Philips Institute of Oral and Craniofacial Molecular Biology
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Contact: Alaina Schneider
afschneider@vcu.edu
804-628-4578
Virginia Commonwealth University
Source:Eurekalert  

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