G-quadruplex stabilization via small molecules as a potential anti-cancer strategy.

G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA or RNA sequences, predominantly located at telomeric ends and within the promoter regions of oncogenes. These structures play essential roles in maintaining telomere stability, regulating DNA replication, and modulating gene transcription and translation. Stabilization of G4 structures can induce cellular senescence and apoptosis while suppressing oncogene expression, positioning them as highly promising therapeutic targets in anticancer research. In recent years, a variety of small-molecule G4 ligands have been developed, many of which exhibit potent antitumor activity by selectively stabilizing G4s. Targeting G4s has thus emerged as a cutting-edge strategy in cancer therapy, offering new avenues for precision medicine. This review provides a comprehensive overview of G4 structure and function, highlights recent progress in the development of G4-targeting ligands, and discusses their therapeutic potential in oncology. Our goal is to offer insights into the design and application of G4-targeted agents for future anticancer drug development.