TRAIL Agonists on Clinical Trials for Cancer Therapy: The Promises and the Challenges

被引:129
作者
Bellail, Anita C. [1 ]
Qi, Ling [1 ]
Mulligan, Patrick [1 ]
Chhabra, Vaninder [2 ]
Hao, Chunhai [1 ]
机构
[1] Emory Univ, Sch Med, Dept Pathol & Lab Med, Atlanta, GA 30322 USA
[2] Emory Univ, Sch Med, Dept Neurosurg, Atlanta, GA USA
基金
加拿大健康研究院;
关键词
Apoptosis; cancer; death receptor; monoclonal antibody; TRAIL;
D O I
10.2174/157488709787047530
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is normally expressed in the human immune system and plays a critical role in antitumor immunity. TRAIL interacts with the death receptors, DR4 and DR5, and activates intracellular apoptotic pathway in cancer cells. This discovery has resulted in a rapid development of cancer therapeutic agents that can activate this apoptotic pathway. These therapeutic agents include recombinant human TRAIL (rhTRAIL) and its agonistic monoclonal antibody (MAb) against DR4 and DR5. Phase I trials have established the safety and tolerability of these TRAIL agonists in patients. Phase II trials are currently evaluating the therapeutic efficacy of TRAIL agonists as single agents or in combination with established cancer therapeutics. This review outlines the advances and the challenges in the development of these TRAIL agonists as effective clinical cancer therapeutics.
引用
收藏
页码:34 / 41
页数:8
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