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胶质瘤中的端粒酶逆转录酶(TERT)启动子突变:在肿瘤发生、转移、诊断、预后、治疗靶点及耐药性中的分子作用

TERT promoter mutations in gliomas: Molecular roles in tumorigenesis, metastasis, diagnosis, prognosis, therapeutic targeting, and drug resistance.

作者信息

Murugan Avaniyapuram Kannan, Kannan Siddarth, Alzahrani Ali S

机构信息

Department of Molecular Oncology, King Faisal Specialist Hospital and Research Centre, Riyadh 11211, Saudi Arabia.

School of Medicine, University of Central Lancashire, Preston PR1 2HE, UK.

出版信息

Biochim Biophys Acta Rev Cancer. 2025 Feb;1880(1):189243. doi: 10.1016/j.bbcan.2024.189243. Epub 2024 Dec 12.

Abstract

Telomerase reverse transcriptase (TERT), a critical player in cellular immortalization, has emerged as a focal point of investigation due to its frequent promoter mutations in various human malignancies. TERT promoter mutations exhibit a significant role in tumorigenesis, fostering unbridled cellular proliferation and survival. This comprehensive review delves into the landscape of TERT promoter mutations and their profound implications in cancer, particularly within the context of gliomas. This article meticulously examines the intricate interplay between TERT promoter mutations and the metastatic cascade, shedding light on their capacity to orchestrate invasive behavior in gliomas. Moreover, this review describes the recent trends in therapeutic targeting of the TERT and dissects the evolving landscape of drug resistance associated with TERT mutations, providing insights into potential therapeutic challenges. In addition, the diagnostic and prognostic implications of TERT promoter mutations in gliomas are scrutinized, unraveling their potential as robust biomarkers. It also discusses the recent advancements in molecular diagnostics, illustrating the promise of TERT mutations as diagnostic tools and prognostic indicators. This review collectively aims to contribute to a deeper understanding of TERT promoter mutations in gliomas, offering a foundation for future research endeavors and paving the way for innovative strategies in glioma management.

摘要

端粒酶逆转录酶(TERT)是细胞永生化的关键因子,由于其在多种人类恶性肿瘤中频繁发生启动子突变,已成为研究的焦点。TERT启动子突变在肿瘤发生中发挥着重要作用,促进细胞无节制地增殖和存活。这篇综述深入探讨了TERT启动子突变的情况及其在癌症中的深远影响,尤其是在胶质瘤的背景下。本文详细研究了TERT启动子突变与转移级联之间的复杂相互作用,揭示了它们在胶质瘤中协调侵袭行为的能力。此外,本综述描述了TERT治疗靶向的最新趋势,并剖析了与TERT突变相关的耐药性不断变化的情况,为潜在的治疗挑战提供了见解。此外,还仔细审查了TERT启动子突变在胶质瘤中的诊断和预后意义,揭示了它们作为强大生物标志物的潜力。它还讨论了分子诊断的最新进展,说明了TERT突变作为诊断工具和预后指标的前景。本综述的总体目标是有助于更深入地了解胶质瘤中的TERT启动子突变,为未来的研究工作提供基础,并为胶质瘤管理的创新策略铺平道路。

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