Ukrainskaya V M, Stepanov A V, Glagoleva I S, Knorre V D, Belogurov A A Jr, Gabibov A G
M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry, Miklukho-Maklaya Str., 16 /10, Russian Academy of Sciences, Moscow, 117997, Russia.
Institute of Fundamental Medicine and Biology, Kremlyovskaya Str., 18, Kazan Federal University, Kazan, 420008, Russia.
Acta Naturae. 2017 Jul-Sep;9(3):55-63.
This article offers a detailed review of the current approaches to anticancer therapy that target the death receptors of malignant cells. Here, we provide a comprehensive overview of the structure and function of death receptors and their ligands, describe the current and latest trends in the development of death receptor agonists, and perform their comparative analysis. In addition, we discuss the DR4 and DR5 agonistic antibodies that are being evaluated at various stages of clinical trials. Finally, we conclude by stating that death receptor agonists may be improved through increasing their stability, solubility, and elimination half-life, as well as by overcoming the resistance of tumor cells. What's more, effective application of these antibodies requires a more detailed study of their use in combination with other anticancer agents.
本文详细综述了目前针对恶性细胞死亡受体的抗癌治疗方法。在此,我们全面概述了死亡受体及其配体的结构和功能,描述了死亡受体激动剂的当前和最新发展趋势,并进行了比较分析。此外,我们还讨论了正在不同临床试验阶段进行评估的DR4和DR5激动性抗体。最后,我们得出结论,死亡受体激动剂可通过提高其稳定性、溶解性和消除半衰期,以及克服肿瘤细胞的耐药性来加以改进。此外,有效应用这些抗体需要更详细地研究它们与其他抗癌药物联合使用的情况。