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用于癌症治疗的金属基分子:从实验室到临床应用

Metal-based molecules in the treatment of cancer: From bench to bedside.

作者信息

Bernal Giuliano, Aquea Gisela, Ramírez-Rivera Sebastián

机构信息

Laboratory of Molecular and Cellular Biology of Cancer, Department of Biomedical Sciences, Faculty of Medicine, Universidad Católica del Norte, Coquimbo, 1781421, Chile.

出版信息

Oncol Res. 2025 Mar 19;33(4):759-779. doi: 10.32604/or.2024.057019. eCollection 2025.

Abstract

Cancer remains one of the leading causes of death in the world, with more than 9 million deaths in 2022, a number that continues to rise. This highlights the urgent need for the development of new drugs, with enhanced antitumor capabilities and fewer side effects. Metal-based drugs have been used in clinical practice since the late 1970s, beginning with the introduction of cisplatin. Later, two additional platinum-based molecules, carboplatin, and oxaliplatin, were introduced, and all three continue to be widely used in the treatment of various cancers. However, despite their significant anticancer activity, the undesirable side effects of these drugs have motivated the scientific community to explore other metal-based complexes with greater anticancer potential and fewer adverse effects. In this context, metals such as ruthenium, copper, gold, zinc, palladium, or iridium, present promising alternatives for the development of new anticancer agents. Unfortunately, although thousands of metal-based drugs have been synthesized and tested both and in animal models, only a few ruthenium-based drugs have entered clinical trials in recent years. Meanwhile, many other molecules with comparable or even greater anticancer potential have not advanced beyond the laboratory stage. In this review, we will revisit the mechanisms of action and anticancer activities of established platinum-based drugs and explore their use in recent clinical trials. Additionally, we will examine the development of potential new metal-based drugs that could one day contribute to cancer treatment worldwide.

摘要

癌症仍然是全球主要死因之一,2022年有超过900万人死于癌症,且这一数字还在持续上升。这凸显了开发新型药物的迫切需求,这类药物需具备更强的抗肿瘤能力且副作用更少。自20世纪70年代末顺铂问世以来,金属基药物就已应用于临床实践。后来,又引入了另外两种铂基分子,即卡铂和奥沙利铂,这三种药物至今仍广泛用于治疗各种癌症。然而,尽管这些药物具有显著的抗癌活性,但其不良副作用促使科学界探索其他具有更大抗癌潜力且副作用更少的金属基配合物。在此背景下,钌、铜、金、锌、钯或铱等金属为开发新型抗癌药物提供了有前景的替代方案。不幸的是,尽管已经合成并在体外和动物模型中测试了数千种金属基药物,但近年来只有少数几种钌基药物进入了临床试验阶段。与此同时,许多其他具有相当甚至更大抗癌潜力的分子尚未走出实验室阶段。在这篇综述中,我们将重新审视已有的铂基药物的作用机制和抗癌活性,并探讨它们在近期临床试验中的应用。此外,我们还将研究潜在的新型金属基药物的开发情况,这些药物未来可能会为全球癌症治疗做出贡献。

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