Telomeres, telomerase and oral cancer (Review).
Oral squamous cell carcinoma (oral cancer) and many squamous cell carcinomas of the head and neck arise as a consequence of multiple molecular events induced by the effects of various carcinogens related to tobacco use, environmental factors, and viruses in some instances (e.g., mucosal oncogenic human papillomaviruses), against a background of inheritable resistance or susceptibility. Consequent genetic damage affects many chromosomes and genes, and it is the accumulation of these changes that appears to lead to carcinoma. Telomere maintenance by telomerase or, in its absence, alternative lengthening of telomeres protect this acquired altered genetic information ensuring immortality without losing eukaryotic linear DNA; when this does not occur DNA is lost and end-replication problems arise. Telomerase is reactivated in 80-90% of cancers thus attracting the attention of pathologists and clinicians who have explored its use as a target for anticancer therapy and to develop better diagnostic and prognostic markers. In the last few years, valuable research from various laboratories has provided major insights into telomerase and telomeres leading to their use as diagnostic and prognostic markers in several types of cancer. Moreover, many strategies have emerged which inhibit this complex enzyme for anticancer therapy and are one step ahead of clinical trials. This review explains the basic biology and the clinical implications of telomerase-based diagnosis and prognosis, the prospects for its use in anticancer therapy, and the limitations it presents in the context of oral cancer.
Sebastian
Sinto
S
Clinical Experimental Oncology Laboratory, Surgery Department, National Cancer Institute, 70126 Bari, Italy.
Grammatica
Luciano
L
Paradiso
Angelo
A
D006801:Humans; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000201:enzymology / Q000235:genetics / Q000628:therapy*; D011379:Prognosis; D019098:Telomerase / Q000378:metabolism*; D016615:Telomere / Q000235:genetics*
D019098:Telomerase