title: Metastatic melanoma treatment: Combining old and new therapies.
abstract: Metastatic melanoma is an aggressive form of cancer characterised by poor prognosis and a complex etiology. Until 2010, the treatment options for metastatic melanoma were very limited. Largely ineffective dacarbazine, temozolamide or fotemustine were the only agents in use for 35 years. In recent years, the development of molecularly targeted inhibitors in parallel with the development of checkpoint inhibition immunotherapies has rapidly improved the outcomes for metastatic melanoma patients. Despite these new therapies showing initial promise; resistance and poor duration of response have limited their effectiveness as monotherapies. Here we provide an overview of the history of melanoma treatment, as well as the current treatments in development. We also discuss the future of melanoma treatment as we go beyond monotherapies to a combinatorial approach. Combining older therapies with the new molecular and immunotherapies will be the most promising way forward for treatment of metastatic melanoma.
authors.affiliation: Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, NSW, Australia.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Davey
authors.affiliation: Department of Medical Oncology, Calvary Mater Hospital, Newcastle, NSW, Australia.
authors.forename: Andre
authors.initials: A
authors.lastname: van der Westhuizen
authors.affiliation: Hunter Medical Research Institute and School of Biomedical Sciences and Pharmacy, Faculty of Health, University of Newcastle, NSW, Australia. Electronic address: Nikola.Bowden@newcastle.edu.au.
authors.forename: Nikola A
authors.initials: NA
authors.lastname: Bowden
mesh_terms: D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D006801:Humans; D007167:Immunotherapy; D016219:Immunotherapy, Adoptive; D007376:Interleukin-2 / Q000627:therapeutic use; D008545:Melanoma / Q000188:drug therapy* / Q000556:secondary; D008565:Membrane Proteins / Q000037:antagonists & inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D058990:Molecular Targeted Therapy; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000235:genetics; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors
chemical_list: D007376:Interleukin-2; D008565:Membrane Proteins; D061026:Programmed Cell Death 1 Receptor; D048493:Proto-Oncogene Proteins B-raf; D020929:Mitogen-Activated Protein Kinase Kinases; D051059:PTEN Phosphohydrolase; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human
keywords: Combination therapy; Immunotherapy; Melanoma; Targeted therapy; Treatment