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TOP2A相关恶性肿瘤及靶向药物的研究进展(综述)

Advances in research on malignant tumors and targeted agents for TOP2A (Review).

作者信息

Zhou Tao, Niu Yiting, Li Yanjun

机构信息

Department of Hepatobiliary Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, Shanxi 030032, P.R. China.

出版信息

Mol Med Rep. 2025 Feb;31(2). doi: 10.3892/mmr.2024.13415. Epub 2024 Dec 13.

Abstract

The DNA topoisomerase isoform topoisomerase IIα (TOP2A) is essential for the condensation and segregation of cellular mitotic chromosomes and the structural maintenance. It has been demonstrated that TOP2A is highly expressed in various malignancies, including lung adenocarcinoma (LUAD), hepatocellular carcinoma (HCC) and breast cancer (BC), associating with poor prognosis and aggressive tumor behavior. Additionally, TOP2A has emerged as a promising target for cancer therapy, with widespread clinical application of associated chemotherapeutic agents. The present study explored the impact of TOP2A on malignant tumor growth and the advancements in research on its targeted drugs. The fundamental mechanisms of TOP2A have been detailed, its specific roles in tumor cells are analyzed, and its potential as a biomarker for tumor prognosis and therapeutic targeting is highlighted. Additionally, the present review compiles findings from the latest clinical trials of relevant targeted agents, information on newly developed inhibitors, and discusses future research directions and clinical application strategies in cancer therapy, aiming to propose novel ideas and methods.

摘要

DNA拓扑异构酶同工型拓扑异构酶IIα(TOP2A)对于细胞有丝分裂染色体的凝聚、分离及结构维持至关重要。已有研究表明,TOP2A在包括肺腺癌(LUAD)、肝细胞癌(HCC)和乳腺癌(BC)在内的多种恶性肿瘤中高表达,与预后不良及侵袭性肿瘤行为相关。此外,TOP2A已成为癌症治疗的一个有前景的靶点,相关化疗药物已广泛应用于临床。本研究探讨了TOP2A对恶性肿瘤生长的影响及其靶向药物的研究进展。详细阐述了TOP2A的基本机制,分析了其在肿瘤细胞中的具体作用,并强调了其作为肿瘤预后生物标志物和治疗靶点的潜力。此外,本综述汇集了相关靶向药物最新临床试验的结果、新开发抑制剂的信息,并讨论了癌症治疗的未来研究方向和临床应用策略,旨在提出新的思路和方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7587/11653171/bb1ad7b3d29a/mmr-31-02-13415-g00.jpg

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