Evaluating the Effect of HDAC8 Inhibition in Malignant Peripheral Nerve Sheath Tumors.
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.
['Lopez|Gonzalo|G|', 'Pollock|Raphael E|RE|']
D000818:Animals D000970:Antineoplastic Agents D017209:Apoptosis D002453:Cell Cycle D045744:Cell Line, Tumor D005260:Female D015972:Gene Expression Regulation, Neoplastic D056572:Histone Deacetylase Inhibitors D006655:Histone Deacetylases D006801:Humans D006877:Hydroxamic Acids D007211:Indoles D051379:Mice D016513:Mice, SCID D018317:Nerve Sheath Neoplasms D012097:Repressor Proteins D047368:Tumor Burden D023041:Xenograft Model Antitumor Assays
HDAC8 Malignant peripheral nerve sheath tumor MPNST Histone deacetylase HDAC HDAC inhibitor