Telomerase as a promising target for human cancer gene therapy.
A number of different approaches have been developed to target human cancer on the basis of its specific expression of telomerase activity. The most common approach relies on inhibition of telomerase activity for reversion of the immortal phenotype of tumor cells. Different components and types of inhibitors targeting various regulatory levels have been regarded as useful for telomerase inhibition. Most methods, however, rely on successive telomere shortening. This process is very slow and causes a long time lag between the onset of inhibition and the occurrence of senescence or apoptosis as a reversal of the immortal phenotype. Many telomerase inhibitors seem to be most efficient when combined with conventional chemotherapeutics. There are some promising approaches to circumvent the slow track of telomere shortening and induce fast apoptosis in treated tumor cells. It has been demonstrated that telomerase may be involved in triggering apoptosis, but the underlying molecular mechanism remains unclear. Other important strategies are the use of telomerase promoters for the application of toxic or pro-apoptotic drugs into human cancer cells or the use of immunological properties of the telomerase enzyme for possible cancer therapies.
Gerontology, Institute of Ageing and Health, Newcastle University, UK.
Gabriele
G
Saretzki
Thomas
T
von Zglinicki
D017209:Apoptosis / Q000187:drug effects; D016503:Drug Delivery Systems; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D007167:Immunotherapy; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D011401:Promoter Regions, Genetic; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics
D004791:Enzyme Inhibitors; D019098:Telomerase