title: [Melanoma: from molecular studies to the treatment breakthrough].
abstract: Melanoma holds a leading position in the mortality from skin tumors. Standard treatment of metastatic melanoma allows tumor remission to be achieved only in a small subset of patients. Studies on melanoma molecular pathogenesis led to the identification of several causative genetic events and, consequently, to the development of novel targeted drugs. More than a half of melanomas contain amine acid substitutions in serine-threonine kinase BRAF. Clinical trials involving specific BRAF inhibitors--vemurafenib and dabrafenib--demonstrated high efficacy of these agents towards BRAF-mutated melanoma. MEK inhibitors may show activity against both BRAF--and NRAS-driven tumors. Mucosal and acral melanomas frequently contain mutation in KIT receptor and can be successfully treated by imatinib. There are novel therapeutic monoclonal antibodies targeted against immunosuppressive molecules CTLA4, PD-1 and PD-L1. In some instances these drugs allow to obtain exceptionally prolonged responses. Whole genome sequencing led to the identification of new melanoma genes, e.g. GRIN2A, TRRAP, PREX2, RAC1, STK19, PPP6C, etc. Molecular testing, especially BRAF mutation analysis, has become a mandatory part of melanoma diagnosis. Nevertheless, despite the revolution in melanoma treatment, the prevention of excessive ultraviolet exposure, cancer awareness and early diagnosis remain the main tools for the management of this disease.
authors: E N
authors: EN
authors: Imianitov
mesh_terms: D001549:Benzamides / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D006801:Humans; D000068877:Imatinib Mesylate; D007093:Imidazoles / Q000008:administration & dosage; D007211:Indoles / Q000008:administration & dosage; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D010091:Oximes / Q000008:administration & dosage; D010879:Piperazines / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D019009:Proto-Oncogene Proteins c-kit / Q000037:antagonists & inhibitors / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D013449:Sulfonamides / Q000008:administration & dosage; D000077484:Vemurafenib
chemical_list: D001549:Benzamides; D007093:Imidazoles; D007211:Indoles; D010091:Oximes; D010879:Piperazines; D011743:Pyrimidines; D013449:Sulfonamides; D000077484:Vemurafenib; D000068877:Imatinib Mesylate; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; C561627:dabrafenib