Division of Pulmonary, Critical Care and Sleep Disorders Medicine, Louisville School of Medicine, Louisville, KY 40202, USA.
Curr Cancer Drug Targets. 2010 Sep;10(6):566-74. doi: 10.2174/156800910791859461.
Lung carcinoma is the leading cause of carcinoma death in the world. Despite recent advances in understanding the molecular biology of lung cancer and the introduction of new therapeutic agents for its treatment, its dismal 5-year survival rate has not changed substantially. Clinical approaches have not significantly improved the survival of patients with advanced lung cancer. However, recent discoveries about the molecular mechanisms responsible for lung cancer initiation and proliferation have unveiled new targets for therapy. One of the hallmark features of cancer cells is their ability to evade programmed cell death or apoptosis. Alterations in pro- and anti-apoptotic pathways are common in cancer cells and defects in regulation of apoptosis have been implicated in both lung tumorigenesis and drug resistance. Thus, targeting apoptosis through the direct or indirect manipulation of the pro-apoptotic machinery offers a novel strategy for treatment. This mini review summaries the molecular events that contribute to drug-induced apoptosis and how lung tumors evade apoptotic death followed by an analysis of the implications for treatment.
肺癌是世界上导致癌症死亡的主要原因。尽管近年来对肺癌的分子生物学有了更多的了解，并引入了新的治疗药物，但肺癌 5 年生存率并没有显著提高。临床方法并没有显著改善晚期肺癌患者的生存。然而，最近对导致肺癌发生和增殖的分子机制的发现，为治疗提供了新的靶点。癌细胞的一个显著特征是它们逃避程序性细胞死亡或细胞凋亡的能力。在癌细胞中，促凋亡和抗凋亡途径的改变很常见，凋亡调节的缺陷与肺肿瘤发生和耐药性有关。因此，通过直接或间接操纵促凋亡机制来靶向细胞凋亡为治疗提供了一种新的策略。这篇迷你综述总结了导致药物诱导细胞凋亡的分子事件，以及肺癌如何逃避细胞凋亡死亡，随后分析了其对治疗的影响。
