pci-34051 and Nerve-Sheath-Neoplasms

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.

Topics: Animals; Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Histone Deacetylase Inhibitors; Histone Deacetylases; Humans; Hydroxamic Acids; Indoles; Mice; Mice, SCID; Nerve Sheath Neoplasms; Repressor Proteins; Tumor Burden; Xenograft Model Antitumor Assays