Penn State Hershey Medical Center, Penn State Hershey Cancer Institute, Penn State College of Medicine, Department of Medicine (Hematology/Oncology), Laboratory of Translational Oncology and Experimental Cancer Therapeutics, Hershey, PA 17033, USA.
Expert Opin Ther Targets. 2010 Oct;14(10):1091-108. doi: 10.1517/14728222.2010.519701.
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family of cytokines, which can induce apoptotic cell death in a variety of tumor cells by engaging specific death receptors, TRAIL-R1 and TRAIL-R2, while having low toxicity towards normal cells. There is interest in cancer therapy inducing cell death by activation of the death-receptor-mediated apoptotic pathway while avoiding decoy-receptor-mediated neutralization of the signal. This has led to the development of a number of receptor-specific TRAIL-variants and agonistic antibodies. Some of these soluble recombinant TRAIL and agonist antibodies targeting TRAIL-R1 and/or TRAIL-R2 are progressing in clinical trials. In addition, TRAIL-resistant tumors can be sensitized to TRAIL by a combination of TRAIL or agonistic antibodies with chemotherapeutic agents, targeted small molecules or irradiation.
Recent advances in developing TRAIL or its agonist receptor antibodies in cancer therapy. We also discuss combination therapies in overcoming TRAIL resistance in cancer cells.
Knowledge of current clinical trials, the promise and obstacles in the future development of therapies affecting TRAIL signaling pathways.
Cancer therapeutics targeting the TRAIL/TRAIL receptor signaling pathway hold great promise for molecularly targeted pro-apoptotic anti-cancer therapy.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）是肿瘤坏死因子细胞因子家族的一员，它可以通过与特定的死亡受体 TRAIL-R1 和 TRAIL-R2 结合，诱导多种肿瘤细胞发生凋亡性细胞死亡，而对正常细胞的毒性较低。人们对通过激活死亡受体介导的凋亡途径诱导细胞死亡而避免诱饵受体介导的信号中和的癌症治疗方法很感兴趣。这导致了许多受体特异性 TRAIL 变体和激动性抗体的发展。其中一些针对 TRAIL-R1 和/或 TRAIL-R2 的可溶性重组 TRAIL 和激动性抗体正在临床试验中进行研究。此外，通过 TRAIL 或激动性抗体与化疗药物、靶向小分子或辐射联合使用，可以使 TRAIL 耐药肿瘤对 TRAIL 敏感。
开发 TRAIL 或其激动性受体抗体用于癌症治疗的最新进展。我们还讨论了克服癌细胞中 TRAIL 耐药性的联合治疗方法。
了解影响 TRAIL 信号通路的当前临床试验、未来治疗发展的前景和障碍。
针对 TRAIL/TRAIL 受体信号通路的癌症治疗方法为分子靶向促凋亡抗癌治疗提供了巨大的前景。
