Technische Universität München, Klinikum rechts der Isar, II. Medizinische Klinik, München, Germany.
J Cell Mol Med. 2010 Jun;14(6A):1255-63. doi: 10.1111/j.1582-4934.2009.00974.x. Epub 2009 Nov 19.
Pancreatic ductal adenocarcinoma (PDAC) is a dismal disease with a median survival below 6 months and a 5-year survival rate below 1%. Effective therapies for locally advanced or metastatic tumours are missing and curatively resected patients relapse in over 80% of the cases. Although histone deacetylases (HDACs) are involved in the control of proliferation, apoptosis, differentiation, migration and angiogenesis of cancer cells, knowledge about the expression patterns and functions of individual HDAC isoenzymes in pancreatic cancer is sparse. This review summarizes the roles of HDACs as novel therapeutic targets and the molecular mode of action of HDAC-inhibitors (HDACI) in PDACs. Success of HDACI in clinical settings will depend on an increased knowledge of HDAC functions as well as on a better understanding of the mode of action of HDACI. Pre-clinical experimental data that constitute the basis for rational therapeutic strategies to treat PDAC are described here. Translating these rational-based therapies into the clinic will finally increase our chance to establish an effective HDACI-containing combination therapy effective against PDAC.
胰腺导管腺癌 (PDAC) 是一种预后极差的疾病，中位生存期不足 6 个月，5 年生存率低于 1%。对于局部晚期或转移性肿瘤，缺乏有效的治疗方法，超过 80%的经根治性切除的患者会复发。尽管组蛋白去乙酰化酶 (HDACs) 参与了癌细胞的增殖、凋亡、分化、迁移和血管生成的控制，但关于单个 HDAC 同工酶在胰腺癌中的表达模式和功能的知识还很匮乏。本文综述了 HDAC 作为新型治疗靶点以及 HDAC 抑制剂 (HDACI) 在 PDAC 中的分子作用模式。HDACI 在临床应用中的成功将取决于对 HDAC 功能的深入了解，以及对 HDACI 作用模式的更好理解。这里描述了构成治疗 PDAC 的合理治疗策略基础的临床前实验数据。将这些基于合理的治疗方法转化为临床应用，最终将增加我们建立有效的针对 PDAC 的含 HDACI 联合治疗的机会。
