Department of Epidemiology and Public Health, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore, Republic of Singapore.
Cancer Lett. 2012 Jan 1;314(1):8-23. doi: 10.1016/j.canlet.2011.09.040. Epub 2011 Oct 7.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been intensively studied as a cancer therapeutic agent due to its unique ability to induce apoptosis in malignant cells but not in normal cells. However, as more human cancer cells are reported to be resistant to TRAIL treatment, it is important to develop new therapeutic strategies to overcome this resistance. p53 is an important tumor suppressor that is widely involved in cellular responses to various stresses. In this mini-review, we aim to provide an overview of the intricate relationship between p53 and the TRAIL-mediated apoptosis pathway, and to summarize the current approaches of targeting p53 as a therapeutic strategy to sensitize TRAIL-induced apoptosis in human cancer cells. Although in some cases TRAIL kills cancer cells in a p53-independent manner, it is believed that in cancers with wild-type and functional p53, targeting p53 may be an important strategy for overcoming TRAIL-resistance in cancer therapy.
肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）因其能够诱导恶性细胞凋亡而不诱导正常细胞凋亡的独特能力而被深入研究为一种癌症治疗剂。然而，随着越来越多的人类癌细胞被报道对 TRAIL 治疗产生耐药性，开发新的治疗策略来克服这种耐药性非常重要。p53 是一种重要的肿瘤抑制因子，广泛参与细胞对各种应激的反应。在这篇迷你综述中，我们旨在提供 p53 与 TRAIL 介导的凋亡途径之间复杂关系的概述，并总结目前靶向 p53 作为一种治疗策略的方法，以增加 TRAIL 诱导的人类癌细胞凋亡的敏感性。尽管在某些情况下，TRAIL 以不依赖 p53 的方式杀死癌细胞，但人们认为，在具有野生型和功能型 p53 的癌症中，靶向 p53 可能是克服癌症治疗中 TRAIL 耐药性的重要策略。
