Targeted inhibition of telomerase in human cancer: will it be a double-edged sword?
More than 80% of human malignancies express telomerase activity, while normal somatic tissues in general lack it. During each normal cell division, there is a constant loss of DNA sequences at chromosomal ends, which is due to the 'end-replication problem' of conventional DNA polymerase. Critical shortening of telomeres induces cell cycle arrest and eventually cell death. Telomerase, a ribonucleoprotein complex with a RNA (TR) and a catalytic subunit (TERT) as core components, is able to add reitineratedly telomeric repeat sequences to the very ends of chromosomes. It was suggested that activation of telomerase in tumor cells has a major impact on their continuous growth. Indeed, transfection of TERT constructs into various normal human cell types led to telomere elongation or stabilization and, most importantly, cellular immortalization. Conversely, inhibition of telomerase in tumor cell lines induced growth arrest, at least in first experimental settings. Such initial success implies that drug-mediated abrogation of telomerase action might be an ideal adjuvant treatment for cancer patients. There are, however, legitimate concerns about the generalization of such an approach.
Sasgary
S
S
Institut für Tumorbiologie-Krebsforschung, Universität Wien.
Wieser
M
M
Cerni
C
C
D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology
D004791:Enzyme Inhibitors; D019098:Telomerase