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Tufts researchers identify a novel target for cancer therapy

Who: Daniel Jay, PhD, Brenda K. Eustace, Takashi Sakurai, Jean K. Stewart, Dean Yimlamai - Department of Physiology, Tufts University School of Medicine, Boston, MA

What: Tufts University researchers and colleagues have discovered an extracellular form of heat shock protein 90 (hsp90) and shown its role in cancer invasion.

Where: Published in Nature Cell Biology Volume 6, 2004

When: June, 2004

Why: Invasion is a key step in tumor progression that eventually leads to metastases when a disseminated tumor cell penetrates through the extracellular matrix and establishes a secondary tumor site elsewhere.

To date there are no effective and safe treatments against metastases due to the lack of reliable validated drug targets. Hsp90 recently has gained significant attention as an important target for cancer therapeutics and hsp90 inhibitors are currently in Phase I and II clinical trials. Since hsp90 is also a key protein for normal cell function, there is some concern about treatment-related toxicity, especially if hsp90 inhibitors are unable to distinguish normal and cancer cells.

In the published article entitled "Functional Proteomic Screens Reveal an Essential Extracellular Role for Hsp90a in Cancer Cell Invasiveness," the researchers used a functional screen on the cell surface proteome of a highly invasive human tumor cell line. The screen identified the extracellular hsp90 associated with tumor cell invasion.

The researchers demonstrated a direct physical and functional interaction between hsp90 and matrix metalloproteinase 2 (MMP2), a primary player in the tumor invasion process. This opens the possibility for developing antibodies against hsp90 for the treatment of cancer.

"This work highlights the relevance of validating function at the protein level. Genetic approaches would have missed the discovery of the novel mechanism of hsp90 action" said Daniel Jay,
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Contact: Peggy Hayes
peggy.hayes@tufts.edu
617-636-3707
Tufts University
1-Jun-2004


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