氮胞苷（azacitidine，甲基化抑制剂）和entinostat（组蛋白去乙酰酶抑制剂）治疗难治

这两类药 已经上市了吗？

近年来，HDAC抑制剂与EGFR抑制剂联合应用治疗NSCLC方面得到了关注。临床前期试验表明HDAC抑制剂可使已对EGFR抑制剂产生耐药性的多种肺癌细胞系重获敏感，并减少EGFR抑制剂的用量，HDAC抑制剂与EGFR抑制剂可协同诱导肺癌细胞的凋亡。

这个HDAC抑制剂是指的什么呀？

Nature Reviews Clinical Oncology 2, 150-157 (March 2005)
Drug Insight: histone deacetylase inhibitors—development of the new targeted anticancer agent suberoylanilide hydroxamic acid
William Kevin Kelly & Paul A Marks

Abstract
This review focuses on the discovery and development of the histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxamic acid (SAHA). Post-translational modifications of the histones of chromatin are important factors in regulating gene expression—so-called epigenetic gene regulation. Acetylation and deacetylation of lysine residues in histone tails, controlled by the activities of HDACs and histone acetyltransferases, are among the most studied post-translational modification of histones. In addition to chromatin protein, transcription factors, cell-signaling regulatory proteins, and proteins regulating cell death are substrates of HDACs and may be altered in function by HDAC inhibitors. HDAC inhibitors have several remarkable aspects. For instance, despite HDACs being ubiquitously distributed through chromatin, SAHA selectively alters the transcription of relatively few genes, and normal cells are at least 10-fold more resistant than transformed cells to SAHA and related HDAC inhibitor-induced cell death. HDAC inhibitors represent a relatively new group of targeted anticancer compounds, which are showing significant promise as agents with activity against a broad spectrum of neoplasms, at doses that are well tolerated by cancer patients. SAHA is one of the HDAC inhibitors most advanced in development. It is in phase I and II clinical trials for patients with both hematologic and solid tumors.