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Nucleic Acids as Therapeutic Targets and Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Finally, therapies involving a combination of telomerase inhibition with other classes of anticancer agents have been studied in order to enhance anticancer efficacy. For example, there is some evidence that imatinib, a selective BCR-ABL tyrosine kinase inhibitor, can enhance telomerase inhibition in cancer cells containing a dominant-negative form of human telomerase (DN-hTERT). Also, telomestatin, a natural telomerase-inhibiting compound from Streptomyces anulatus (Figure 5.80), has been shown to increase the sensitivity of some cancer cell lines to imatinib and agents with different mechanisms of action such as daunorubicin, mitoxantrone, and vincristine.
Telomerase: a good target in hepatocellular carcinoma? An overview of relevant preclinical data
Published in Expert Opinion on Therapeutic Targets, 2022
Maria Lina Tornesello, Anna Lucia Tornesello, Noemy Starita, Andrea Cerasuolo, Francesco Izzo, Luigi Buonaguro, Franco Maria Buonaguro
The G‑rich 3′ single strand overhang is a telomeric region forming G-quadruplex structures precluding telomerase elongation. Several ligands have been characterized that stabilize the G‑quadruplex structures and block telomerase access. Telomestatin is the most studied G4-quadruplex ligand and it was shown to induce telomere shortening and to inhibit proliferation in leukemia cells in vitro as well as in a xenograft tumor model [117,118]. The gradual attrition of telomeres and eventual crisis in human cancer cells was reached with non-toxic doses of Telomestatin, while higher doses induced DNA damage responses and acute cell death [119]. A major issue with the G‑quadruplex ligands as anti-cancer agents is their affinity to non-telomeric G‑rich DNA sequences, which may cause high toxicity in normal cells [118]. No published study has investigated the effect of Telomestatin in liver cancer cells.