title: Non-BRAF-targeted therapy, immunotherapy, and combination therapy for melanoma.
abstract: BACKGROUND
  Melanoma is an aggressive disease characterized by a complex etiology. The discovery of key driving mutations (primarily BRAF mutations) led to the development of specific molecular inhibitors providing clinical benefit.
  
  
  METHODS
  Although BRAF-specific drugs have perhaps yielded the best results in melanoma-targeted therapy, there still remain several limitations, mostly due to the emergence of resistance and the lack of efficacy in patients without BRAF mutation. Novel drugs are currently being tested in clinical trials and showed encouraging results. Such drugs can specifically target molecular pathways aberrantly activated or repressed during melanoma development (targeted therapy) or act in a way to enhance the host immune system to fight cancer (immunotherapy). Here we provide a detailed overview of the current clinical strategies, which lay beyond BRAF-targeted therapy, spanning from molecular-targeted therapy to immunotherapy and to combination therapy.
  
  
  CONCLUSIONS
  Major advances in our understanding of the mechanisms behind melanoma development have led to the implementation of novel therapeutic drugs. Unfortunately, tools allowing prediction of responsiveness to a given treatment are not available yet. The increasing availability of high-throughput technologies will allow the elucidation of molecular mechanisms underlying responsiveness to cancer therapy and unveil an increased number of potential therapeutic targets.
authors.affiliation: National Institutes of Health, Clinical Center and trans-NIH Center for Human Immunology (CHI), Department of Transfusion Medicine, Infectious Disease and Immunogenetics Section (IDIS) , Bethesda, MD 20892 , USA bedognettid@cc.nih.gov.
authors.forename: Sara
authors.initials: S
authors.lastname: Tomei
authors.forename: Ena
authors.initials: E
authors.lastname: Wang
authors.forename: Lucia Gemma
authors.initials: LG
authors.lastname: Delogu
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Marincola
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
mesh_terms: D019496:Cancer Vaccines / Q000008:administration & dosage; D006801:Humans; D007167:Immunotherapy; D008545:Melanoma / Q000473:pathology / Q000628:therapy*; D009362:Neoplasm Metastasis; D048493:Proto-Oncogene Proteins B-raf / Q000187:drug effects*
chemical_list: D019496:Cancer Vaccines; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf