MOE Key Laboratory of Bioinorganic and Synthetic Chemistry, School of Chemistry, State Key Laboratory of Oncology in South China, Sun Yat-Sen University, Guangzhou 510275, P. R. China.
Chem Soc Rev. 2023 Apr 24;52(8):2790-2832. doi: 10.1039/d2cs00757f.
The great clinical success of cisplatin and its derivatives has convinced people that metal complexes could play a more significant role in human cancer therapy. However, targeting and drug resistance are still two dominant problems that need to be urgently solved for metallodrugs' efficacy and clinical translation. As an important component of metal complexes, organometallics have been experiencing rapid development in recent years. Compared with platinum drugs, emerging anti-tumor organometallics targeting dynamic bioprocesses provide an effective strategy to overcome conventional problems. This review focuses on burgeoning anti-tumor strategies and provides up-to-date advances in anti-tumor organometallics development based on their action mechanisms. Specifically, important tumor-overexpressed proteins and nucleic acids as organometallics' anti-tumor targets are systematically presented, followed by organometallics that exert their anti-tumor activity by perturbing tumor intracellular energy/redox/metal/immune homeostasis. Finally, nine cell death pathways including apoptosis, paraptosis, autophagy, oncosis, necrosis, necroptosis, ferroptosis, pyroptosis, and immunogenic cell death (ICD) that can be induced by organometallics are reviewed, and their morphological and biochemical features are summarised. This review at the interface of chemistry, biology, and medicine aims to enlighten the rational development of organometallic anti-tumor agents.
顺铂及其衍生物的巨大临床成功使人们相信金属配合物可以在人类癌症治疗中发挥更重要的作用。然而，对于金属药物的疗效和临床转化，靶向和耐药性仍然是两个需要迫切解决的主要问题。作为金属配合物的重要组成部分，有机金属近年来发展迅速。与铂类药物相比，针对动态生物过程的新型抗肿瘤有机金属为克服传统问题提供了一种有效的策略。本文综述了新兴的抗肿瘤策略，并根据作用机制介绍了抗肿瘤有机金属发展的最新进展。具体而言，系统地介绍了肿瘤过表达蛋白和核酸等重要的肿瘤靶标作为有机金属的抗肿瘤靶点，然后介绍了通过干扰肿瘤细胞内能量/氧化还原/金属/免疫平衡发挥抗肿瘤活性的有机金属。最后，综述了有机金属可以诱导的 9 种细胞死亡途径（细胞凋亡、副凋亡、自噬、胀亡、坏死、坏死性凋亡、铁死亡、细胞焦亡和免疫原性细胞死亡），并总结了它们的形态和生化特征。本文旨在化学、生物学和医学之间架起一座桥梁，为有机金属抗肿瘤药物的合理开发提供启示。
