Departamento de Bioquímica, Biología Molecular y Celular, Universidad de Zaragoza, Zaragoza, Spain.
Biochem Pharmacol. 2012 Jun 1;83(11):1475-83. doi: 10.1016/j.bcp.2011.12.036. Epub 2012 Jan 2.
Apo 2 ligand/tumor necrosis factor (TNF)-related apoptosis-inducing ligand (Apo2L/TRAIL), is a member of the TNF family of cytokines, which can induce apoptotic cell death in cells expressing at least one of their specific death receptors, DR4 (TRAIL-R1) or DR5 (TRAIL-R2). In the last decade, the Apo2L/TRAIL system of apoptosis has attracted significant interest as a potential drug-targeting pathway for human therapy, due to the ability of that cytokine to trigger apoptosis in various types of cancer cells while displaying low or no toxicity to normal cells. Recent results suggest that manipulating the Apo2L/TRAIL system may be also useful for the treatment of inflammatory disorders such as rheumatoid arthritis. For its possible therapeutic use, a number of receptor-specific Apo2L/TRAIL molecular variants and agonistic monoclonal antibodies have been developed, and some of them are in clinical trials. In addition, Apo2L/TRAIL-resistant tumors can be sensitized to Apo2L/TRAIL by selected novel or classical chemotherapeutic agents, opening new possibilities for combined therapies. We will briefly review the current status of Apo2L/TRAIL-based therapies for human disease, their promises and limitations.
载脂蛋白 2 配体/肿瘤坏死因子（TNF）相关凋亡诱导配体（Apo2L/TRAIL）是 TNF 细胞因子家族的一员，它可以诱导至少表达其特定死亡受体之一的细胞发生凋亡性细胞死亡，DR4（TRAIL-R1）或 DR5（TRAIL-R2）。在过去的十年中，Apo2L/TRAIL 凋亡系统因其能够在各种类型的癌细胞中引发凋亡，而对正常细胞显示低毒性或无毒性，因此作为人类治疗的潜在药物靶向途径引起了极大的兴趣。最近的结果表明，操纵 Apo2L/TRAIL 系统对于治疗类风湿关节炎等炎症性疾病也可能有用。为了可能的治疗用途，已经开发了许多受体特异性的 Apo2L/TRAIL 分子变体和激动性单克隆抗体，其中一些正在临床试验中。此外，通过选择新型或经典化学治疗剂，可以使 Apo2L/TRAIL 耐药肿瘤对 Apo2L/TRAIL 敏感，为联合治疗开辟了新的可能性。我们将简要回顾基于 Apo2L/TRAIL 的人类疾病治疗方法的现状、它们的前景和局限性。
