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Heat shock proteins in cancer: targeting the ‘chaperones’

    Z Nahleh

    * Author for correspondence

    Division of Hematology-Oncology, Department of Internal Medicine, TTUHSC-Paul L. Foster School of Medicine, 4800 Alberta Avenue, El Paso, TX 79905, USA.

    ,
    A Tfayli

    American University of Beirut Medical Center, PO Box 11-0236, Riad El Solh, Beirut 1107 2020, Beirut, Lebanon

    ,
    A Najm

    MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX 77030, USA

    ,
    A El Sayed

    Memorial Medical Center, 2450 S. Telshor Blvd, Las Cruces, NM 88011, USA

    &
    Z Nahle

    Vanderbilt University Medical Center, T-4224 MCN, Nashville, TN 37232, USA

    Published Online:https://doi.org/10.4155/fmc.12.50

    Heat shock proteins (Hsps) are highly conserved proteins working as molecular chaperones for several cellular proteins essential for normal cell viability and growth, and have numerous cytoprotective roles. The expression of Hsps is induced in response to a wide variety of physiological and environmental stress insults, including anticancer chemotherapy, thus allowing the cell to survive lethal conditions. Cancer cells experience high levels of proteotoxic stress and rely upon stress-response pathways for survival and proliferation, thereby becoming dependent on proteins such as stress-inducible Hsps. Owing to the implication of Hsps in cancer, Hsp inhibition has recently emerged as an interesting potential anticancer strategy. Many natural and synthetic Hsp inhibitors molecular compounds are in development and many are being evaluated as potential cancer therapies. One of the Hsps in particular, Hsp90, has several client proteins and is emerging as a particularly exciting cancer target due to the prospect of simultaneously inhibiting chaperoning of numerous oncogenic proteins. This review describes the function of Hsps focusing on current efforts in exploiting the attributes of Hsps as potential targets for anticancer therapy.

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