title: [Cellular and molecular mechanisms of carcinogenic side effects and resistance to BRAF inhibitors in metastatic melanoma with BRAFV600 mutation: state of the knowledge].
abstract: Cutaneous melanoma is a malignant tumor with a high metastatic potential. If an early treatment is associated with a favorable outcome, the prognosis of metastatic melanoma remains poor. Advances in molecular characterization of cancers, notably the discovery of BRAF gene mutations in metastatic melanoma, allowed to the recent development of targeted therapies against mutated BRAF protein. Despite high tumor response rates observed in clinical trials, these new drugs are associated with frequent secondary tumor resistance occurrence and paradoxical carcinogenic side effects. The cellular and molecular mechanisms of these carcinogenic side effects and secondary resistance are not yet fully elucidated and are actually intensely studied. This review of the literature focus on the mechanisms of these carcinogenic side effects and on the tumor resistance associated with anti-BRAF targeted therapies.
authors: Service de pathologie, centre François-Baclesse, 3, avenue Général-Harris, BP 5026, 14076 Caen cedex 05, France. Electronic address: m.capovilla@baclesse.unicancer.fr.
authors: Mathieu
authors: M
authors: Capovilla
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D004789:Enzyme Activation / Q000187:drug effects; D044127:Epigenesis, Genetic; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D007211:Indoles / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007636:Keratoacanthoma / Q000139:chemically induced; D007938:Leukemia / Q000139:chemically induced*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008545:Melanoma / Q000139:chemically induced / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000556:secondary*; D008954:Models, Biological; D058990:Molecular Targeted Therapy; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D016609:Neoplasms, Second Primary / Q000139:chemically induced*; D014411:Neoplastic Stem Cells / Q000201:enzymology; D009508:Nevus, Pigmented / Q000201:enzymology / Q000473:pathology; D017354:Point Mutation; D047428:Protein Kinase Inhibitors / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D019908:Proto-Oncogene Proteins c-raf / Q000096:biosynthesis / Q000502:physiology; D012878:Skin Neoplasms / Q000139:chemically induced*; D013449:Sulfonamides / Q000009:adverse effects* / Q000494:pharmacology* / Q000627:therapeutic use; D059016:Tumor Microenvironment; D000077484:Vemurafenib
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D009363:Neoplasm Proteins; D047428:Protein Kinase Inhibitors; D013449:Sulfonamides; D000077484:Vemurafenib; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D019908:Proto-Oncogene Proteins c-raf
keywords: BRAF(V600) mutation; Carcinogenesis; Carcinogenèse; Metastatic melanoma; Mutation BRAF(V600); Mélanome métastatique; Resistance; Résistance; Targeted therapy; Thérapie ciblée