Department of Pharmacy, University of Naples Federico II, Naples, Italy.
Expert Opin Ther Pat. 2023 Nov;33(11):745-773. doi: 10.1080/13543776.2023.2271168. Epub 2024 Jan 11.
Guanine-rich DNA sequences can fold into four-stranded noncanonical secondary structures called G-quadruplexes (G4s) which are widely distributed in functional regions of the human genome, such as telomeres and gene promoter regions. Compelling evidence suggests their involvement in key genome functions such as gene expression and genome stability. Notably, the abundance of G4-forming sequences near transcription start sites suggests their potential involvement in regulating oncogenes.
This review provides an overview of current knowledge on G4s in human oncogene promoters. The most representative G4-binding ligands have also been documented. The objective of this work is to present a comprehensive overview of the most promising targets for the development of novel and highly specific anticancer drugs capable of selectively impacting the expression of individual or a limited number of genes.
Modulation of G4 formation by specific ligands has been proposed as a powerful new tool to treat cancer through the control of oncogene expression. Actually, most of G4-binding small molecules seem to simultaneously target a range of gene promoter G4s, potentially influencing several critical driver genes in cancer, thus producing significant therapeutic benefits.
富含鸟嘌呤的 DNA 序列可以折叠成称为 G-四链体 (G4s) 的非经典四级结构，它们广泛分布于人类基因组的功能区域，如端粒和基因启动子区域。有强有力的证据表明它们参与了关键的基因组功能，如基因表达和基因组稳定性。值得注意的是，转录起始位点附近 G4 形成序列的丰富性表明它们可能参与调节致癌基因。
本综述提供了人类致癌基因启动子中 G4 的最新知识概述。也记录了最具代表性的 G4 结合配体。这项工作的目的是全面概述最有前途的靶点，以开发新型和高度特异性的抗癌药物，能够选择性地影响单个或少数基因的表达。
通过控制致癌基因表达，特定配体对 G4 形成的调节被提议作为一种治疗癌症的强大新工具。实际上，大多数 G4 结合小分子似乎同时靶向一系列基因启动子 G4，可能影响癌症中的几个关键驱动基因，从而产生显著的治疗益处。
