Targeted inhibition of telomerase in human cancer: Will it be a double-edged sword?

More than 80% of human malignancies express telomerase activity, while norm al somatic tissues in general lack it. During each normal cell division, th ere is a constant loss of DNA sequences at chromosomal ends, which is due t o the 'end-replication problem' of conventional DNA polymerase. Critical sh ortening of telomeres induces cell cycle arrest and eventually cell death. Telomerase, a ribonucleoprotein complex with a RNA (TR) and a catalytic sub unit (TERT) as core components, is able to add reitineratedly telomeric rep eat sequences to the very ends of chromosomes. It was suggested that activa tion of telomerase in tumor cells has a major impact on their continuous gr owth. Indeed, transfection of TERT constructs into various normal human cel l types led to telomere elongation or stabilization and, most importantly, cellular immortalization. Conversely, inhibition of telomerase in tumor cel l lines induced growth arrest, at least in first experimental settings. Suc h initial success implies that drug-mediated abrogation of telomerase actio n might be an ideal adjuvant treatment for cancer patients. There are, howe ver, legitimate concerns about the generalization of such an approach.