Telomere

Telomeres are specialized nucleoprotein structures consisting of tandem TTAGGG repeats located at the terminal ends of eukaryotic chromosomes. Their primary biological function is to protect chromosome ends from degradation and prevent them from being recognized as double-stranded DNA breaks, a process mediated by the shelterin protein complex (Shay, J. W., 2016, Seminars in Cancer Biology). In normal somatic cells, telomeres progressively shorten during each round of DNA replication due to the end-replication problem, eventually triggering cellular senescence or apoptosis. In contrast, approximately 85-90% of cancer cells maintain their telomeres through the reactivation of telomerase, a ribonucleoprotein enzyme, enabling replicative immortality and sustained tumor growth (Herbert, B. S., et al., 2005, Nature Reviews Cancer). Therapeutic strategies targeting telomeres include telomerase inhibitors like Imetelstat, which binds to the hTR template, and G-quadruplex stabilizers like CX-5461 that disrupt telomere capping and induce a rapid DNA damage response (Neidle, S., 2017, Nature Reviews Chemistry). These interventions aim to exhaust the proliferative capacity of cancer cells while minimizing impact on normal tissues, although hematologic toxicities remain a significant clinical challenge.

Other names

Chromosomal endsTTAGGG repeatsTelomeric DNATerminal hexanucleotide repeats

Inhibition of telomere maintenance through telomerase antagonism or stabilization of G-quadruplex structures to induce telomere uncapping and a DNA damage response.