Telomerase inhibition and the future management of head-and-neck cancer.
Telomeres are tandem repeats of DNA associated with specific proteins. These structures cap eukaryotic chromosomes and maintain the integrity of the chromosome ends. In the germline, telomeres are maintained by the enzyme telomerase, but in normal somatic cells the enzyme's activity is low or undetectable. Human tumours, including squamous-cell carcinoma of the head and neck (SCCHN), need telomerase to maintain telomere function; inhibition of the enzyme can lead to apoptosis. Furthermore, because most tumour cells have very short telomeres, they are more likely to succumb to telomerase inhibition than normal cells. Telomerase is therefore a potential selective anticancer target. The telomere is also involved in the repair of DNA double strand breaks, and telomere dysfunction provokes radiosensitivity. In this review we consider whether manipulation of telomere function may selectively sensitise SCCHN to radiotherapy and discuss the possible pitfalls. We also assess how some conventional treatments may affect the subsequent use of telomerase inhibitors.
McCaul
James A
JA
Maxillofacial surgery, Beatson Institute for Cancer Research, Glasgow, UK. jim.mccaul@ntlworld.com
Gordon
Katrina E
KE
Clark
Louise J
LJ
Parkinson
E Kenneth
EK
D002294:Carcinoma, Squamous Cell / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000201:enzymology / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D019098:Telomerase / Q000037:antagonists & inhibitors*; D016615:Telomere / Q000528:radiation effects
D004791:Enzyme Inhibitors; D019098:Telomerase