Telomeres rather than telomerase a key target for anti-cancer therapy?
It was in the 1930s that telomeres (from the Greek telos = end and meros = part) were first recognized as essential structures at the ends of the chromosomes and were shown to be important for chromosomal stability (Muller HJ: The remaking of chromosomes. The Collecting Net-Woods Hole 1938: 13: 181-198, McClintock B, The stability of broken ends of chromosomes in Zea mays. Genetics 1041: 26: 234-282). However, it was only in 1978 that the first telomeric sequence was identified -- in the protocoa Tetrahymena, a single cell organism that at a certain stage of development has many identical minichromosomes with twice as many telomeres (Blackburn EH and Gall JG. A tandemly repeated sequence at the termini of the extrachromosomal ribosomal RNA genes in Tetrahymena. J. Mol. Biol. 1978: 120: 33-53.). Today we know that telomeres form specialized, three-dimensional DNA-protein structures and fulfil important capping functions. Besides, telomeric DNA is essential as ''access DNA'' for those cells that are not able to counteract loss of DNA during replication because they do not express telomerase, the enzyme responsible for telomere length maintenance. Since telomerase is mostly found in tumor cells and inhibition correlates with telomere shortening and finally growth inhibition, telomerase and lately also the telomeres themselves have become attractive targets for anti-cancer therapy. This review aims to critically throw light on different therapeutical approaches and comes to the conclusion that telomeres may be the better targets for cancer therapeutics.
Boukamp
Petra
P
Department of Genetics and Skin Carcinogenesis, German Cancer Research Center, Heidelberg, Germany. p.boukamp@dkfz.de
Mirancea
Nicolas
N
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology; D019098:Telomerase / Q000187:drug effects / Q000378:metabolism*; D016615:Telomere / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D019098:Telomerase