title: The Future of Molecular Analysis in Melanoma: Diagnostics to Direct Molecularly Targeted Therapy.
abstract: Melanoma is a malignancy of pigment-producing cells that is driven by a variety of genetic mutations and aberrations. In most cases, this leads to upregulation of the mitogen-activated protein kinase (MAPK) pathway through activating mutations of upstream mediators of the pathway including BRAF and NRAS. With the advent of effective MAPK pathway inhibitors, including the US FDA-approved BRAF inhibitors vemurafenib and dabrafenib and MEK inhibitor trametinib, molecular analysis has become an integral part of the care of patients with metastatic melanoma. In this article, the key molecular targets and strategies to inhibit these targets therapeutically are presented, and the techniques of identifying these targets, in both tissue and blood, are discussed.
authors.affiliation: Department of Medicine, Metrowest Medical Center, Framingham, MA, USA.
authors.forename: Hugo
authors.initials: H
authors.lastname: Akabane
authors.affiliation: Center for Melanoma, Massachusetts General Hospital Cancer Center, 55 Fruit Street, Boston, MA, 02114, USA. rsullivan7@mgh.harvard.edu.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Sullivan
mesh_terms: D004252:DNA Mutational Analysis; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors; D048370:MAP Kinase Kinase 2 / Q000037:antagonists & inhibitors; D020935:MAP Kinase Signaling System; D008545:Melanoma / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D025202:Molecular Diagnostic Techniques; D058990:Molecular Targeted Therapy; D009154:Mutation; D010091:Oximes / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D011728:Pyridones / Q000627:therapeutic use; D011744:Pyrimidinones / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use; D000077484:Vemurafenib
chemical_list: D007093:Imidazoles; D007211:Indoles; D008565:Membrane Proteins; D010091:Oximes; D047428:Protein Kinase Inhibitors; D011728:Pyridones; D011744:Pyrimidinones; D013449:Sulfonamides; D000077484:Vemurafenib; C560077:trametinib; C482128:MAP2K2 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D048369:MAP Kinase Kinase 1; D048370:MAP Kinase Kinase 2; C482125:MAP2K1 protein, human; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human; C561627:dabrafenib