Lopez Gonzalo, Pollock Raphael E
Division of Surgical Oncology, James Comprehensive Cancer Center, The Ohio State University, N-924 Doan Hall, 410W. 10th Avenue, Columbus, OH, 43210-1228, USA.
Methods Mol Biol. 2017;1510:365-374. doi: 10.1007/978-1-4939-6527-4_27.
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.
恶性外周神经鞘瘤（MPNST）是一种侵袭性很强的疾病，预后很差。该疾病可散发性发生，也可发生于患有遗传性神经纤维瘤病（NF-1）的患者。MPNST通常对治疗干预有抗性。因此，有必要改进治疗方法。几种广谱组蛋白去乙酰化酶（HDAC）抑制剂对I类HDAC亚型具有高亲和力。抑制多种HDAC亚型通常会导致不良副作用，而抑制单一亚型可能会改善治疗窗口并限制毒性。最近，HDAC8抑制剂已被开发出来，在最初的临床前研究中，它们显示出抗癌功效。关于HDAC8在MPNST中的作用知之甚少。我们最近在人和小鼠MPNST模型中揭示了HDAC8抑制的抗癌作用。我们先前研究的目的是确定HDAC8抑制在MPNST中的潜在治疗效果。在本章中，我们简要描述了确定药理学HDAC抑制在MPNST中的作用的方法。
