title: Emerging targeted therapies for melanoma.
abstract: BACKGROUND
  Melanoma is an aggressive cutaneous malignancy associated with poor response to traditional therapies. Recent regulatory approval for immune checkpoint inhibitors and agents targeting mutated BRAF has led to a tremendous expansion of effective treatment options for patients with advanced melanoma. Unfortunately, primary or acquired resistance develops in most patients, highlighting the need for additional therapies. Numerous genetic and other molecular features of this disease may provide effective targets for therapy development.
  
  
  METHODS
  This article reviews available melanoma treatments, including immune and molecularly-targeted therapies. We then discuss agents in development, with a focus on targeted (rather than immune) therapies. In particular, we discuss agents that block mitogen-activated protein kinase (MAPK) signaling, as well as other emerging approaches such as antibody-drug conjugates, cell-cycle targeting, and novel genetically-informed clinical trials.
  
  
  CONCLUSIONS
  Despite the incredible advances in melanoma therapeutics over the last several years, a clear need to develop more effective therapies remains. Molecularly-targeted therapy approaches will likely remain a cornerstone of melanoma treatment in parallel to immune therapy strategies.
authors.affiliation: a Department of Medicine , Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center , Nashville , TN , USA.
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Johnson
authors.affiliation: b Department of Pharmacology , Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center , Nashville , TN , USA.
authors.forename: Megan H
authors.initials: MH
authors.lastname: Pollack
authors.affiliation: a Department of Medicine , Vanderbilt University Medical Center and Vanderbilt Ingram Cancer Center , Nashville , TN , USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Sosman
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015195:Drug Design; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; KIT; Melanoma; NRAS; binimetinib; cobimetinib; glembatumumab vedotin; imatinib; targeted therapy; trametinib