On the Road to Fight Cancer: The Potential of G-Quadruplex Ligands as Novel Therapeutic Agents

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.

Automated summary

G-quadruplex-forming nucleic acid sequences are highly present in the human genome and have been evolutionarily selected for their pivotal role in cell biology. Targeting G-quadruplexes in cancer has shown potential therapeutic benefits, with small molecules stabilizing these structures demonstrating antitumor activity in preclinical models. Further research is needed to fully understand the biological implications and develop effective G-quadruplex-based anticancer strategies.