[Role of epigenetics in the carcinogenesis of head and neck carcinomas - possible new targeted therapy?].
In search of new targeted therapies for squamous cell carcinoma of the head neck (HNSCC), a better understanding of the carcinogenesis is of outmost importance. Recent studies show that not only genetic but also epigenetic alterations initiate the multistep process of tumordevelopment. Epigenetic changes lead to altered gene expression without alterations of the DNA sequence. The best characterized epigenetic change is the methylation of the promoter region of genes, especially of tumorsuppressor genes. The methylation of the promoter region blocks the promoter and therefore represses transcription. The loss of the gene products of tumorsuppressor genes leads to increased proliferation and decreased apoptosis. Methylation of tumorsuppressor genes was shown in precancerous lesions of HNSCC, which emphasizes the importance of methylation as an early biomarker. Several studies of tumor cell cultures show reactivated expression of proteins and as a result reduction of proliferation and induction of apoptosis after treatment with demethylating agentens. This presents a very promising new option for a targeted therapy.
Weber
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Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Plastische Operationen, Universitätsklinikum Leipzig, Leipzig. Anette.Weber@medizin.unileipzig.de
Dietz
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Tischoff
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Tannapfel
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D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors; D000077209:Decitabine; D044127:Epigenesis, Genetic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D016153:Genes, Suppressor / Q000187:drug effects; D010039:Otorhinolaryngologic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D052416:Targeted Gene Repair / Q000379:methods*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine