Snajdauf Martin, Havlova Klara, Vachtenheim Jiri, Ozaniak Andrej, Lischke Robert, Bartunkova Jirina, Smrz Daniel, Strizova Zuzana
Third Department of Surgery, First Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czechia.
Department of Urology, Second Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czechia.
Front Mol Biosci. 2021 Mar 10;8:628332. doi: 10.3389/fmolb.2021.628332. eCollection 2021.
TRAIL (tumor-necrosis factor related apoptosis-inducing ligand, CD253) and its death receptors TRAIL-R1 and TRAIL-R2 selectively trigger the apoptotic cell death in tumor cells. For that reason, TRAIL has been extensively studied as a target of cancer therapy. In spite of the promising preclinical observations, the TRAIL-based therapies in humans have certain limitations. The two main therapeutic approaches are based on either an administration of TRAIL-receptor (TRAIL-R) agonists or a recombinant TRAIL. These approaches, however, seem to elicit a limited therapeutic efficacy, and only a few drugs have entered the phase II clinical trials. To deliver TRAIL-based therapies with higher anti-tumor potential several novel TRAIL-derivates and modifications have been designed. These novel drugs are, however, mostly preclinical, and many problems continue to be unraveled. We have reviewed the current status of all TRAIL-based monotherapies and combination therapies that have reached phase II and phase III clinical trials in humans. We have also aimed to introduce all novel approaches of TRAIL utilization in cancer treatment and discussed the most promising drugs which are likely to enter clinical trials in humans. To date, different strategies were introduced in order to activate anti-tumor immune responses with the aim of achieving the highest efficacy and minimal toxicity.In this review, we discuss the most promising TRAIL-based clinical trials and their therapeutic strategies.
肿瘤坏死因子相关凋亡诱导配体（TRAIL，CD253）及其死亡受体TRAIL-R1和TRAIL-R2可选择性地触发肿瘤细胞的凋亡性细胞死亡。因此，TRAIL作为癌症治疗靶点已得到广泛研究。尽管临床前观察结果很有前景，但基于TRAIL的人类治疗存在一定局限性。两种主要治疗方法分别基于给予TRAIL受体（TRAIL-R）激动剂或重组TRAIL。然而，这些方法似乎疗效有限，只有少数药物进入了II期临床试验。为了提供具有更高抗肿瘤潜力的基于TRAIL的治疗方法，人们设计了几种新型TRAIL衍生物和修饰物。然而，这些新型药物大多处于临床前阶段，许多问题仍有待解决。我们回顾了所有已进入人类II期和III期临床试验的基于TRAIL的单一疗法和联合疗法的现状。我们还旨在介绍TRAIL在癌症治疗中的所有新应用方法，并讨论了可能进入人类临床试验的最有前景的药物。迄今为止，人们引入了不同策略来激活抗肿瘤免疫反应，以实现最高疗效和最小毒性。在本综述中，我们讨论了最有前景的基于TRAIL的临床试验及其治疗策略。
