Division of Gastroenterology, Endocrinology and Metabolism, Philipps University Marburg, Baldinger Strasse, Marburg, Germany.
Curr Pharm Biotechnol. 2012 Sep;13(11):2273-82. doi: 10.2174/138920112802501953.
Pancreatic cancer constitutes one of the most aggressive tumours with a 5-year survival rate of less than 5%. It is characterized by a high degree of resistance to apoptosis which is associated by high expression levels of multiple prosurvival proteins of the extrinsic and intrinsic apoptosis signalling cascades. This review focuses on current knowledge of apoptotic pathways involved in pancreatic cancer and mechanisms of resistance to apoptosis, including alterations in the death receptor and mitochondrial pathways, as well as anti-apoptotic effects of NF-kB and Akt signalling and the impact of histone-modifying enzymes such as histondeacetylases (HDAC). Furthermore, the therapeutic implications of modulating pro-survival pathways by specific inhibitors investigated in preclinical and clinical trials will be discussed.
胰腺癌是最具侵袭性的肿瘤之一，其 5 年生存率低于 5%。它的特点是对细胞凋亡具有高度的抵抗力，这与外在和内在细胞凋亡信号通路中多种生存蛋白的高表达水平有关。本综述重点介绍了参与胰腺癌细胞凋亡的凋亡途径和抗细胞凋亡机制的最新知识，包括死亡受体和线粒体途径的改变，以及 NF-κB 和 Akt 信号的抗细胞凋亡作用，以及组蛋白修饰酶如组蛋白脱乙酰酶（HDAC）的影响。此外，还将讨论通过临床前和临床试验中研究的特定抑制剂来调节生存途径的治疗意义。
