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端粒酶相关因子 1 和 2:基于端粒的癌症治疗的开拓性靶点。

TRF1 and TRF2: pioneering targets in telomere-based cancer therapy.

机构信息

Department of Pharmaceutical Technology and Biochemistry, Faculty of Chemistry, Gdansk University of Technology, Gdansk, 80-233, Poland.

Department of Medical Genetics, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

出版信息

J Cancer Res Clin Oncol. 2024 Jul 16;150(7):353. doi: 10.1007/s00432-024-05867-3.

Abstract

This article presents an in-depth exploration of the roles of Telomere Repeat-binding Factors 1 and 2 (TRF1 and TRF2), and the shelterin complex, in the context of cancer biology. It emphasizes their emerging significance as potential biomarkers and targets for therapeutic intervention. Central to the shelterin complex, TRF1 and TRF2 are crucial in maintaining telomere integrity and genomic stability, their dysregulation often being a hallmark of cancerous cells. The article delves into the diagnostic and prognostic capabilities of TRF1 and TRF2 across various cancer types, highlighting their sensitivity and specificity. Furthermore, it reviews current strides in drug discovery targeting the shelterin complex, detailing specific compounds and their modes of action. The review candidly addresses the challenges in developing therapies aimed at the shelterin complex, including drug resistance, off-target effects, and issues in drug delivery. By synthesizing recent research findings, the article sheds light on the intricate relationship between telomere biology and cancer development. It underscores the urgency for continued research to navigate the existing challenges and fully leverage the therapeutic potential of TRF1, TRF2, and the shelterin complex in the realm of cancer treatment.

摘要

本文深入探讨了端粒重复结合因子 1 和 2(TRF1 和 TRF2)以及庇护体复合物在癌症生物学中的作用。强调它们作为潜在生物标志物和治疗干预靶点的重要性日益凸显。TRF1 和 TRF2 是庇护体复合物的核心,对于维持端粒完整性和基因组稳定性至关重要,它们的失调通常是癌细胞的特征。本文深入探讨了 TRF1 和 TRF2 在各种癌症类型中的诊断和预后能力,强调了它们的敏感性和特异性。此外,还回顾了针对庇护体复合物的药物发现的最新进展,详细介绍了特定化合物及其作用模式。该综述坦率地讨论了开发针对庇护体复合物的疗法所面临的挑战,包括耐药性、脱靶效应和药物递送问题。通过综合最近的研究发现,本文阐明了端粒生物学与癌症发展之间的复杂关系。强调了继续研究的紧迫性,以应对现有挑战,并充分利用 TRF1、TRF2 和庇护体复合物在癌症治疗领域的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55db/11793265/dbef5b52fe5e/432_2024_5867_Fig1_HTML.jpg

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