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Heat Shock Protein 90: The Cancer Chaperone

  • Chapter
Heat Shock Proteins in Cancer

Part of the book series: Heat Shock Proteins ((HESP,volume 2))

Abstract

Heat shock protein 90 (Hsp90) is a molecular chaperone required for the stability and function of a number of conditionally activated and/or expressed signaling proteins, as well as multiple mutated, chimeric, and/or over-expressed signaling proteins, that promote cancer cell growth and/or survival. Hsp90 inhibitors are unique in that, although they are directed towards a specific molecular target, they simultaneously inhibit multiple cellular signaling pathways. By inhibiting nodal points in multiple overlapping survival pathways utilized by cancer cells, combination of an Hsp90 inhibitor with standard chemotherapeutic agents may dramatically increase the in vivo efficacy of the standard agent. Hsp90 inhibitors may circumvent the characteristic genetic plasticity that has allowed cancer cells to eventually evade the toxic effects of most molecularly targeted agents. The mechanism-based use of Hsp90 inhibitors, both alone and in combination with other drugs, should be effective toward multiple forms of cancer. Further, because Hsp90 inhibitors also induce Hsf-1-dependent expression of Hsp70, and because certain mutated Hsp90 client proteins are neurotoxic, these drugs display ameliorative properties in several neurodegenerative disease models, suggesting a novel role for Hsp90 inhibitors in treating multiple pathologies involving neurodegeneration

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  1. Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA

    Len Neckers

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  1. Harvard Medical School, Boston, U.S.A

    Stuart K. Calderwood

  2. Boston University School of Medicine, Boston, U.S.A

    Michael Y. Sherman

  3. National Research Council CONICET, Mendoza, Argentina

    Daniel R. Ciocca

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Neckers, L. (2007). Heat Shock Protein 90: The Cancer Chaperone. In: Calderwood, S.K., Sherman, M.Y., Ciocca, D.R. (eds) Heat Shock Proteins in Cancer. Heat Shock Proteins, vol 2. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-6401-2_12

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