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Evaluating the Effect of HDAC8 Inhibition in Malignant Peripheral Nerve Sheath Tumors

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HDAC/HAT Function Assessment and Inhibitor Development

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1510))

Abstract

Malignant peripheral nerve sheath tumor (MPNST) is a highly aggressive disease with a dismal prognosis. The disease can occur sporadically or in patients with inherited neurofibromatosis (NF-1). MPNST is typically resistant to therapeutic intervention. Hence, the need for improved therapies is warranted. Several broad spectrum histone deacetylase (HDAC) inhibitors have a high affinity for class I HDAC isoforms. Inhibition of multiple HDAC isoforms often results in undesirable side effects, while inhibiting a single isoform could possibly improve the therapeutic window and limit toxicity. Recently, HDAC8 inhibitors have been developed and in initial preclinical studies, they demonstrate anticancer efficacy. Little is known about the role of HDAC8 in MPNST. We recently revealed an anticancer effect of HDAC8 inhibition in human and murine MPNST models. The goal of our previous study was to determine the potential therapeutic efficacy of HDAC8 inhibition in MPNST. In this chapter, we briefly describe the methods for determining the role of pharmacological HDAC inhibition in MPNST.

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Acknowledgement

Grant Support: National Cancer Institute SARC Sarcoma SPORE, # U54CA168512.

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Authors and Affiliations

  1. Division of Surgical Oncology, James Comprehensive Cancer Center, The Ohio State University, N-924 Doan Hall, 410W. 10th Avenue, Columbus, OH, 43210-1228, USA

    Gonzalo Lopez & Raphael E. Pollock M.D., Ph.D.

Authors
  1. Gonzalo Lopez
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  2. Raphael E. Pollock M.D., Ph.D.
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Corresponding author

Correspondence to Raphael E. Pollock M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Institute of Toxicology, University Medical Center Mainz, Mainz, Germany

    Oliver H. Krämer

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Lopez, G., Pollock, R.E. (2017). Evaluating the Effect of HDAC8 Inhibition in Malignant Peripheral Nerve Sheath Tumors. In: Krämer, O. (eds) HDAC/HAT Function Assessment and Inhibitor Development. Methods in Molecular Biology, vol 1510. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6527-4_27

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  • DOI: https://doi.org/10.1007/978-1-4939-6527-4_27

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-6525-0

  • Online ISBN: 978-1-4939-6527-4

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