Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins School of Medicine, Baltimore, MD, USA.
Cancer Therapy Evaluation Program, National Cancer Institute, Bethesda, MD, USA.
Future Oncol. 2017 Jun;13(13):1137-1148. doi: 10.2217/fon-2016-0526. Epub 2017 Mar 9.
Entinostat is a synthetic benzamide derivative histone deacetylase (HDAC) inhibitor, which potently and selectively inhibits class I and IV HDAC enzymes. This action promotes histone hyperacetylation and transcriptional activation of specific genes, with subsequent inhibition of cell proliferation, terminal differentiation and apoptosis. This oral HDAC inhibitor has been evaluated in Phase I and II trials in patients with advanced malignancies, and is in general well tolerated. Entinostat does not currently have regulatory approval for clinical use; however promising preclinical and clinical data exist in hormone-resistant breast cancer. An ECOG-ACRIN Phase III registration study is ongoing in advanced breast cancer (E2112, NCT02115282) and aims to confirm the overall survival advantage observed with the combination of exemestane and entinostat/placebo in the Phase II setting (ENCORE301 trial). This article provides an overview of the chemistry, pharmacokinetics/pharmacodynamics and available clinical data for entinostat with a focus on advanced breast cancer.
恩替诺特是一种合成的苯甲酰胺类组蛋白去乙酰化酶（HDAC）抑制剂，能强有力和选择性地抑制 I 类和 IV 类 HDAC 酶。该作用促进组蛋白超乙酰化和特定基因的转录激活，随后抑制细胞增殖、终末分化和细胞凋亡。该口服 HDAC 抑制剂已在晚期恶性肿瘤患者的 I 期和 II 期试验中进行了评估，一般具有良好的耐受性。恩替诺特目前尚未获得临床应用的监管批准；然而，在激素耐药性乳腺癌中存在有前景的临床前和临床数据。ECOG-ACRIN 正在进行一项针对晚期乳腺癌的 III 期注册研究（E2112，NCT02115282），旨在确认在 II 期研究（ENCORE301 试验）中观察到依西美坦联合恩替诺特/安慰剂的总生存优势。本文综述了恩替诺特的化学、药代动力学/药效学和现有临床数据，重点关注晚期乳腺癌。
