EPIGENETIC REGULATION OF GENE EXPRESSION IN HEAD AND NECK SQUAMOUS CELL CARCINOMA: THERAPEUTIC PERSPECTIVES

Abstract

Head and neck tumors (HNT) include cancers of nasal cavity, oral cavity, larynx, pharynx, cervical esophagus, paranasal sinuses, and salivary glands; in most of the cases HNT are presented by squamous cell carcinoma. Despite the fact that tumors of head and neck are generally available for visual inspection, about 60–70 % of the patients are diagnosed with it at advanced (III or IV) stages of the disease. Unfortunately, optimization of diagnostic algorithms and wide implementation of instrumental diagnostics (ultrasound examination, computed tomography, fiber endoscopy) do not improve the situation. Current trends in HNT incidence and mortality in Russia (increasing of both absolute and relative figures of incidence and mortality over the last 10–12 years) clearly demonstrate its social importance. Available epidemiological data suggests the obvious need for fundamental studies devoted to HNT pathogenesis as well as for development of novel meth ods of pathogenetic therapy. Along with the importance of investigation of typical for HNT genetic abnormalities, we should also stress studying of epigenetic regulation disorders in tumor cells because of its particular practical value. This review is aimed to analyze the relationship between different mechanisms of epigenetic regulation of gene expression, and to evaluate this relationship in squamous cell HNT. In terms of new therapy methods development it is important to understand the complex nature of epigenetic control of gene expression as soon as it allows to create and implement optimal methods of chemotherapy. For instance, the antitumor effect of butyric acid could be theoretically modified or enhanced by the inhibitors of miR-17-92a or miR-31 mimics. In this case one of the drugs can be administrated locally, and the other one – systemically, this possibility can help to reach maximum therapeutic effect in the tumor tissue. The main aim of this review was to present mechanisms, development prospects and application possibilities of HNT epigenetic therapy, which can be soon offered to clinicians.