title: Molecular Targeted Therapy Approaches for BRAF Wild-Type Melanoma.
abstract: Patients with metastatic melanoma have historically had dismal outcomes. The last several years has seen the emergence of effective immune and targeted therapies for metastatic melanoma. Targeted therapies have primarily impacted the 40-50% of patients with BRAF(V600) mutated melanoma. The remainder of patients with advanced melanoma harbor a wide spectrum of mutations other than BRAF(V600) that are associated with unique pathophysiological, prognostic, and therapeutic implications. The treatment of this subset of patients is a challenging problem. In recent years, preclinical and early clinical studies have suggested that inhibitors of mitogen activated protein kinase (MAPK) pathway and parallel signaling networks may have activity in treatment of BRAF(V600) wild-type (WT) melanoma. In this review, we will discuss available and developing therapies for BRAF WT patients with metastatic melanoma, particularly focusing on molecular targeted options for various genetically defined melanoma subsets.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232, USA. Romany.a.johnpulle@vanderbilt.edu.
authors.forename: Romany A N
authors.initials: RA
authors.lastname: Johnpulle
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232, USA. Douglas.b.johnson@vanderbilt.edu.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, 777 Preston Research Building, 2220 Pierce Avenue, Nashville, TN, 37232, USA. Jeff.sosman@vanderbilt.edu.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
mesh_terms: D018572:Disease-Free Survival; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D058990:Molecular Targeted Therapy / Q000379:methods / Q000639:trends; D009154:Mutation / Q000187:drug effects* / Q000235:genetics; D011379:Prognosis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D016896:Treatment Outcome; D014481:United States
chemical_list: D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: Angiogenesis; Atypical; BRAF wild-type; Bevacizumab; Binimetinib; CDK4; CKIT; GNA11; GNAQ; Immunotherapy; Inhibitor; Ipilimumab; MAPK; MEK; Melanoma; Mutation; NF; NRAS; Selumetinib; Trametinib