title: Signalling and chemosensitivity assays in melanoma: is mutated status a prerequisite for targeted therapy?
abstract: Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.
authors.forename: Thierry
authors.initials: T
authors.lastname: Passeron
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Lacour
authors.forename: Maryline
authors.initials: M
authors.lastname: Allegra
authors.forename: Coralie
authors.initials: C
authors.lastname: Ségalen
authors.forename: Anne
authors.initials: A
authors.lastname: Deville
authors.forename: Antoine
authors.initials: A
authors.lastname: Thyss
authors.forename: Damien
authors.initials: D
authors.lastname: Giacchero
authors.forename: Jean-Paul
authors.initials: JP
authors.lastname: Ortonne
authors.forename: Corine
authors.initials: C
authors.lastname: Bertolotto
authors.forename: Robert
authors.initials: R
authors.lastname: Ballotti
authors.forename: Philippe
authors.initials: P
authors.lastname: Bahadoran
mesh_terms: D000293:Adolescent; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001557:Benzenesulfonates / Q000494:pharmacology / Q000627:therapeutic use; D002070:Butadienes / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D003606:Dacarbazine / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D017809:Fatal Outcome; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D009154:Mutation / Q000235:genetics*; D009536:Niacinamide / Q000031:analogs & derivatives; D009570:Nitriles / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010671:Phenylurea Compounds; D010766:Phosphorylation / Q000187:drug effects; D057285:Precision Medicine / Q000379:methods*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects*; D000077157:Sorafenib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D002070:Butadienes; D009570:Nitriles; D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011725:Pyridines; C113580:U 0126; D009536:Niacinamide; D003606:Dacarbazine; D000077157:Sorafenib; D019009:Proto-Oncogene Proteins c-kit; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048049:Extracellular Signal-Regulated MAP Kinases; C054368:fotemustine