Anticancer therapy targeting telomeres and telomerase : current status.
Normal human somatic cells undergo telomeric attrition causing replicative senescence. Most immortal cancer cells cope with this by upregulating the active form of telomerase. Long-term inhibition of telomerase results in telomeric attrition and highly specific killing of cancer cells, in which the maintenance of telomere length is reliant on telomerase activity. Unfortunately, telomere erosion requires many cell divisions, possibly opening the way for acquired drug resistance. Recent attempts to solve this problem include the development of drugs that are more potent catalytic inhibitors, deny telomerase access to the telomere in situ, or affect telomere structure; some of these drugs have entered clinical trials. Combinations of these approaches may ultimately produce the best clinical results. This article reviews the latest results in both basic and applied telomere research that indicate the most promising avenues for future anticancer drug development in this area.
Parkinson
E Kenneth
EK
Queen Mary's School of Medicine and Dentistry, Centre for Clinical and Diagnostic Oral Sciences, Institute of Cell and Molecular Sciences, London, England. e.k.parkinson@qmul.ac.uk
Minty
Fay
F
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012313:RNA / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000187:drug effects* / Q000235:genetics
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase