Telomerase and telomeres: from basic biology to cancer treatment.
The limited capacity to divide is one of the major differences between normal somatic cells and cancerous cells. This 'finite life span' of somatic cells is closely linked to loss of telomeric DNA at telomeres, the 'chromosome caps' consisting of repeated (7TAGGG) sequences., In more than 85% of advanced cancers, this telomeric attrition is compensated by telomerase, 'the immortality enzyme', implying that telomerase inhibition may restore mortality in tumor cells. This review discusses the progress in research on the structure and function of telomeres and the telomerase holoenzyme. In addition, new developments in telomere/telomerase targeting compounds such as antisense oligonucleotides and G-quadruplex stabilizing substances, but also new telomerase expression-related strategies such as telomerase promoter-driven suicide gene therapy and telomerase immunotherapy will be presented. It will be discussed how these data can be implemented in telomerase-directed therapies.
Helder
Marco N
MN
Department of Gynaecological Oncology, University Hospital Groningen, The Netherlands.
Wisman
G Bea A
GB
van der Zee
G J
GJ
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008957:Models, Genetic; D009369:Neoplasms / Q000201:enzymology*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000502:physiology*; D016615:Telomere / Q000502:physiology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D019098:Telomerase