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Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors

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Chaperones

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1709))

Abstract

Inhibitors of the molecular chaperone heat shock protein 90 (Hsp90) have been in clinical development as anticancer agents since 1998. There have been 18 Hsp90 inhibitors (Hsp90i) that have entered the clinic, all of which, though structurally distinct, target the ATP-binding Bergerat fold of the chaperone N-terminus. Currently, there are five Hsp90 inhibitors in clinical trial and no approved drug in this class. One impediment to development of a clinically efficacious Hsp90 inhibitor has been the very low percentage of clinical trials that have codeveloped a predictive or pharmacodynamic marker of the anticancer activity inherent in this class of drugs. Here, we provide an overview of the clinical development of Hsp90 inhibitors, review the pharmacodynamic assays that have been employed in the past, and highlight new approaches to Hsp90 inhibitor clinical development.

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Acknowledgments

This work was supported by the Intramural Research Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health.

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Authors and Affiliations

  1. Developmental Therapeutics Branch, Center for Cancer Research, NCI, NIH, Bethesda, MD, USA

    Akira Yuno, Min-Jung Lee, Sunmin Lee, Yusuke Tomita, David Rekhtman & Brittni Moore

  2. Developmental Therapeutics Branch, CCR, NCI, NIH, Bldg 10, Rm 12C432A, 10 Center Drive, Bethesda, MD, 20892, USA

    Jane B. Trepel

Authors
  1. Akira Yuno
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  2. Min-Jung Lee
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  3. Sunmin Lee
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  4. Yusuke Tomita
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  5. David Rekhtman
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  6. Brittni Moore
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  7. Jane B. Trepel
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Corresponding author

Correspondence to Jane B. Trepel .

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Editors and Affiliations

  1. Department of Radiation, Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

    Stuart K. Calderwood

  2. Department of Urology, Weis Center for Research, Geisinger Clinic, Danville, Pennsylvania, USA

    Thomas L. Prince

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Yuno, A. et al. (2018). Clinical Evaluation and Biomarker Profiling of Hsp90 Inhibitors. In: Calderwood, S., Prince, T. (eds) Chaperones. Methods in Molecular Biology, vol 1709. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7477-1_29

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  • DOI: https://doi.org/10.1007/978-1-4939-7477-1_29

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7476-4

  • Online ISBN: 978-1-4939-7477-1

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