title: Evaluating the Effect of HDAC8 Inhibition in Malignant Peripheral Nerve Sheath Tumors.
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.
authors.affiliation: Division of Surgical Oncology, James Comprehensive Cancer Center, The Ohio State University, N-924 Doan Hall, 410W. 10th Avenue, Columbus, OH, 43210-1228, USA.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Lopez
authors.affiliation: Division of Surgical Oncology, James Comprehensive Cancer Center, The Ohio State University, N-924 Doan Hall, 410W. 10th Avenue, Columbus, OH, 43210-1228, USA. Raphael.pollock@osumc.edu.
authors.forename: Raphael E
authors.initials: RE
authors.lastname: Pollock
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D007211:Indoles / Q000494:pharmacology*; D051379:Mice; D016513:Mice, SCID; D018317:Nerve Sheath Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; C529435:PCI 34051; D012097:Repressor Proteins; C409470:HDAC8 protein, human; D006655:Histone Deacetylases
keywords: HDAC; HDAC inhibitor; HDAC8; Histone deacetylase; MPNST; Malignant peripheral nerve sheath tumor