以杯突症为靶点进行癌症治疗:机理认识与临床展望

IF 29.5 1区 医学 Q1 HEMATOLOGY
Chenliang Zhang, Tingting Huang, Liping Li
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引用次数: 0

摘要

铜中毒是一种新发现的细胞死亡形式,由细胞内铜(Cu)的过度积累诱发。从机理上讲,铜中毒是铜诱导的二氢脂酰胺 S-乙酰转移酶聚集的结果,与线粒体三羧酸循环和铁硫簇蛋白质的损失有关,最终导致蛋白质毒性应激,引发细胞死亡。最近,杯突症作为一种重要的癌症治疗策略在肿瘤研究中引起了极大的兴趣。在这篇综述中,我们总结了杯突症的细胞和分子机制及其与其他类型细胞死亡的关系。此外,我们还综述了目前可用于诱导肿瘤细胞杯突症的药物或策略,包括铜离子诱导剂、小化合物和纳米药物。此外,我们还针对癌症治疗中的细胞代谢和特定调控基因进行了研究,以提高肿瘤对杯突症的敏感性。最后,我们探讨了靶向杯突抑制克服肿瘤化疗和免疫治疗耐药性的可行性,并提出了未来的研究方向。这项研究表明,以杯突症为靶点可以为开发肿瘤疗法开辟新途径。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Targeting cuproptosis for cancer therapy: mechanistic insights and clinical perspectives
Cuproptosis is a newly identified form of cell death induced by excessive copper (Cu) accumulation within cells. Mechanistically, cuproptosis results from Cu-induced aggregation of dihydrolipoamide S-acetyltransferase, correlated with the mitochondrial tricarboxylic acid cycle and the loss of iron–sulfur cluster proteins, ultimately resulting in proteotoxic stress and triggering cell death. Recently, cuproptosis has garnered significant interest in tumor research due to its potential as a crucial therapeutic strategy against cancer. In this review, we summarized the cellular and molecular mechanisms of cuproptosis and its relationship with other types of cell death. Additionally, we reviewed the current drugs or strategies available to induce cuproptosis in tumor cells, including Cu ionophores, small compounds, and nanomedicine. Furthermore, we targeted cell metabolism and specific regulatory genes in cancer therapy to enhance tumor sensitivity to cuproptosis. Finally, we discussed the feasibility of targeting cuproptosis to overcome tumor chemotherapy and immunotherapy resistance and suggested future research directions. This study suggested that targeting cuproptosis could open new avenues for developing tumor therapy.
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来源期刊
CiteScore
48.10
自引率
2.10%
发文量
169
审稿时长
6-12 weeks
期刊介绍: The Journal of Hematology & Oncology, an open-access journal, publishes high-quality research covering all aspects of hematology and oncology, including reviews and research highlights on "hot topics" by leading experts. Given the close relationship and rapid evolution of hematology and oncology, the journal aims to meet the demand for a dedicated platform for publishing discoveries from both fields. It serves as an international platform for sharing laboratory and clinical findings among laboratory scientists, physician scientists, hematologists, and oncologists in an open-access format. With a rapid turnaround time from submission to publication, the journal facilitates real-time sharing of knowledge and new successes.
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