Bellail Anita C, Qi Ling, Mulligan Patrick, Chhabra Vaninder, Hao Chunhai
Department of Pathology & Laboratory Medicine, 1365-C Clifton Road, Atlanta, GA, USA.
Rev Recent Clin Trials. 2009 Jan;4(1):34-41. doi: 10.2174/157488709787047530.
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.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）在人类免疫系统中正常表达，在抗肿瘤免疫中发挥关键作用。TRAIL与死亡受体DR4和DR5相互作用，并激活癌细胞内的凋亡途径。这一发现促使能够激活该凋亡途径的癌症治疗药物迅速发展。这些治疗药物包括重组人TRAIL（rhTRAIL）及其针对DR4和DR5的激动性单克隆抗体（MAb）。I期试验已确定这些TRAIL激动剂在患者中的安全性和耐受性。II期试验目前正在评估TRAIL激动剂作为单一药物或与已有的癌症治疗药物联合使用的治疗效果。本综述概述了这些TRAIL激动剂作为有效的临床癌症治疗药物开发过程中的进展和挑战。
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