Human telomeric G-quadruplex: The current status of telomeric G-quadruplexes as therapeutic targets in human cancer

The 3′‐ends of human chromosomal DNA terminate in short single‐stranded guanine‐rich tandem‐repeat sequences. In cancer cells, these are associated with the telomere‐maintenance enzyme telomerase together with the end‐binding protein hPOT1. Small molecules that can compete with these proteins and induce the single‐stranded DNA to form quadruplex–ligand complexes are, in effect, able to expose these 3′‐ends, which results in the activation of a DNA damage response and selective inhibition of cell growth. Several of these G‐quadruplex binding molecules have shown promising anticancer activity in tumour xenograft models, which indicate that the approach may be applicable to the treatment of a wide range of human cancers. This minireview summarizes the available data on these compounds and the challenges posed for drug discovery.