title: Beyond BRAF: where next for melanoma therapy?
abstract: In recent years, melanoma has become a poster-child for the development of oncogene-directed targeted therapies. This approach, which has been exemplified by the development of small-molecule BRAF inhibitors and the BRAF/MEK inhibitor combination for BRAF-mutant melanoma, has brought new hope to patients. Despite these successes, treatment failure seems near inevitable in the majority of cases—even in individuals treated with the BRAF/MEK inhibitor doublet. In the current review, we discuss the future of combination strategies for patients with BRAF-mutant melanoma as well as the emerging therapeutic options for patients with NRAS-mutant and BRAF/NRAS-wild-type melanoma. We also outline some of the newest developments in the in-depth personalisation of therapy that should allow melanoma treatment to continue shaping the field precision cancer medicine.
authors.affiliation: The Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: I V
authors.initials: IV
authors.lastname: Fedorenko
authors.affiliation: The Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: G T
authors.initials: GT
authors.lastname: Gibney
authors.affiliation: The Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: V K
authors.initials: VK
authors.lastname: Sondak
authors.affiliation: 1] The Department of Molecular Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA [2] The Department of Cutaneous Oncology, The Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL 33612, USA.
authors.forename: K S M
authors.initials: KS
authors.lastname: Smalley
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics; D008565:Membrane Proteins / Q000235:genetics; D058990:Molecular Targeted Therapy; D020125:Mutation, Missense; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D012878:Skin Neoplasms / Q000188:drug therapy / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D008565:Membrane Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human