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Sidestepping cancer's chaperone
Date:10/18/2007

WORCESTER, Mass. Cancerous tumors are wildly unfavorable environments. Struggling for oxygen and nutrients while being bombarded by the bodys defense systems, tumor cells in fact require sophisticated adaptations to survive and grow. For decades, scientists have sought ways to circumvent these adaptations to destroy cancer. Now, researchers at the University of Massachusetts Medical School (UMMS), have defined a method to target and kill cancers chaperonea protein that promotes tumor cell stability and survivalwithout damaging healthy cells nearby.

In Regulation of Tumor Cell Mitochondrial Homeostasis by an Organelle-Specific Hsp90 Chaperone Network, published in the October 19 issue of Cell, Dario C. Altieri, MD, the Eleanor Eustis Farrington Chair in Cancer Research and professor and chair of cancer biology, and colleagues at UMMS, identify a new pathway by which cancer cells grow and surviveand provide a clear blueprint for the design and production of a novel class of anticancer agents aimed squarely at that pathway.

While previous research has demonstrated that a class of proteins known as molecular chaperones promote tumor cell survival, the specific way in which the proteins achieve this has not been well understood. And although inhibitors of a specific chaperone known as heat shock protein 90 (Hsp90) have been studied for the treatment of cancer, progress has been questionable. In this current research, Dr. Altieri and colleagues sought to both define the mechanism by which Hsp90 leads to tumor cell stability and survival, and understand why general suppression of Hsp90 has not been as successful in clinical trials.

Notably, they found a very abundant pool of Hsp90 (and its related molecule TRAP-1) in the mitochondria of tumor cells. Mitochondria are organelles that produce a cells energy, but also play a key role in cell death. Indeed, many current drugs and treatments work by damaging the mitochondria. Data obtained by
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Contact: Kelly Bishop
kelly.bishop@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

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