MOLECULAR GENETIC ASPECTS OF MELANOMA PART 2. MOLECULAR MARKERS FOR TARGET THERAPY

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Issue: 
2
Year: 
2017

L.F. Gulyaeva Ph.D. (Biol.), Professor, Head of the Laboratory of Molecular Mechanisms of Carcinogenesis, Research Institute of Molecular Biology and Biophysics (Novosibirsk) N.N. Mazurenko Ph.D. (Biol.), Professor, Head of the Laboratory of Onkogenomiks Institute of Carcinogenesis, N.N. Blokhin Russian Cancer Research Center Russian (Moscow) N.E. Kushlinskii Ph.D. (Med.), Professor, Corresponding Member of the Russian Academy of Sciences, Head of the Laboratory of Clinical Biochemistry, N.N. Blokhin Russian Cancer Research Center Russian (Moscow)

Melanoma – the most dangerous malignant skin disease with a high risk of recurrence and metastasis. Molecular biological stud-ies carried out in the last decade have dramatically changed our understanding of the mechanisms of melanocyte carcinogenesis. This review describes how hereditary factors predisposing to melanoma (rare mutant alleles of CDKN2A, CDK4, MITF and BAP1 genes) and somatic genetic abnormalities involved in the carcinogenesis of melanocytes. Gene mutations that cause hyperactivation of RAS-MAPK- (KIT, ERBB4, BRAF, NRAS, MEK, NF1) and PI3K- (PTEN, AKT) signaling pathways are analyzed. Also considered is the role of CAMP and NF-κB in melanomagenesis. Identification of mutations in oncogenes activating key signaling pathways has allowed using drugs of targeted actions (Target therapy), many of which showed a good therapeutic effect. The combined treatment with immunotherapy is particularly promising for melanoma.

Keywords: 
melanoma
genetic disorders
RAS-MAPK- and PI3K-signaling pathways
carcinogenesis.

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