Wu Gen Sheng
Karmanos Cancer Institute, Department of Pathology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Cancer Lett. 2009 Nov 18;285(1):1-5. doi: 10.1016/j.canlet.2009.02.029. Epub 2009 Mar 18.
The tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that can initiate apoptosis through the activation of their death receptors. The ability of TRAIL to selectively induce apoptosis of transformed or tumor cells but not normal cells promotes the development of TRAIL-based cancer therapy. Accumulating preclinical studies demonstrate that the TRAIL ligand can effectively induce cancer cell apoptosis. Completed and ongoing Phases I and II clinical trials using TRAIL are showing clinically promising outcomes without significant toxicity. Importantly, TRAIL, DR4 and DR5 can all be induced by chemotherapeutics and/or radiation, which can sensitize cancer cells to TRAIL. Thus, understanding the regulation of the TRAIL apoptosis pathway can help develop more selective TRAIL-based agents for the treatment of human cancer.
肿瘤坏死因子（TNF）相关凋亡诱导配体（TRAIL）是TNF超家族的成员，可通过激活其死亡受体引发凋亡。TRAIL选择性诱导转化细胞或肿瘤细胞而非正常细胞凋亡的能力推动了基于TRAIL的癌症治疗的发展。越来越多的临床前研究表明，TRAIL配体可有效诱导癌细胞凋亡。使用TRAIL的已完成和正在进行的I期和II期临床试验显示出临床前景良好且无明显毒性。重要的是，TRAIL、DR4和DR5均可被化疗药物和/或放疗诱导，这可使癌细胞对TRAIL敏感。因此，了解TRAIL凋亡途径的调控有助于开发更具选择性的基于TRAIL的药物用于治疗人类癌症。
