Department of Applied Research and Technological Development, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Molecular Pharmacology Unit, Via G.A. Amadeo, 42, 20133 Milan, Italy.
Int J Mol Sci. 2021 May 31;22(11):5947. doi: 10.3390/ijms22115947.
Nucleic acid sequences able to adopt a G-quadruplex conformation are overrepresented within the human genome. This evidence strongly suggests that these genomic regions have been evolutionary selected to play a pivotal role in several aspects of cell biology. In the present review article, we provide an overview on the biological impact of targeting G-quadruplexes in cancer. A variety of small molecules showing good G-quadruplex stabilizing properties has been reported to exert an antitumor activity in several preclinical models of human cancers. Moreover, promiscuous binders and multiple targeting G-quadruplex ligands, cancer cell defense responses and synthetic lethal interactions of G-quadruplex targeting have been also highlighted. Overall, evidence gathered thus far indicates that targeting G-quadruplex may represent an innovative and fascinating therapeutic approach for cancer. The continued methodological improvements, the development of specific tools and a careful consideration of the experimental settings in living systems will be useful to deepen our knowledge of G-quadruplex biology in cancer, to better define their role as therapeutic targets and to help design and develop novel and reliable G-quadruplex-based anticancer strategies.
能够采用 G-四链体构象的核酸序列在人类基因组中大量存在。这一证据强烈表明，这些基因组区域已经在进化上被选择来在细胞生物学的几个方面发挥关键作用。在本文综述中，我们概述了靶向癌症中 G-四链体的生物学影响。已经报道了多种具有良好 G-四链体稳定特性的小分子在几种人类癌症的临床前模型中具有抗肿瘤活性。此外，还强调了混杂结合物和多种靶向 G-四链体配体、癌细胞防御反应以及靶向 G-四链体的合成致死相互作用。总的来说，迄今为止收集到的证据表明，靶向 G-四链体可能是癌症治疗的一种创新而有吸引力的方法。持续的方法改进、特定工具的开发以及在活系统中仔细考虑实验设置，将有助于加深我们对癌症中 G-四链体生物学的认识，更好地定义它们作为治疗靶点的作用，并帮助设计和开发新的、可靠的基于 G-四链体的抗癌策略。
