Telomerase in cancer diagnosis and therapy - A clinical perspective

Curing cancers is one of the most challenging tasks of modern medicine. The major problem is the heterogeneity of human tumours and thus finding a 'un iversal' target for cancer treatment. The discovery that the expression of the enzyme telomerase is a hallmark of immortality and cancer, and that it is found in the majority (>85%) of human tumours but is repressed in most n ormal cells, has therefore caused considerable excitement. These observatio ns led to the design of potential telomerase inhibitors and ideas about tar geting telomerase in the clinic. To date, several classes of telomerase inh ibitory agents have been identified and are in preclinical development. How ever, the approach has not yet been tested clinically. Because of the proposed function of telomerase, and the understanding that replicative cell senescence or cell death result from progressive telomere shortening during successive cell divisions, even complete enzyme inhibitio n will not produce immediate cell death. Designing clinical trials for prom ising telomerase inhibitors requires consideration of the novel mechanism o f action of these drugs. A lag period between initiation of treatment and o ccurrence of effects is likely, and thus anti-telomerase therapy might best be given in adjuvant treatment protocols after initial tumour debulking th erapy and in combination with other cytostatic agents. The available knowledge of telomerase biology and its association with huma n tumours suggests that telomerase inhibition might prove a valuable additi on to current cancer treatment regimens.