title: New drug targets in metastatic melanoma.
abstract: Over the past 30 years, and despite extensive clinical research, the treatment options for metastatic melanoma have been limited. Single-agent and combination chemotherapy, hormonal therapy, biochemotherapy, immunotherapy, targeted agent therapy and combination regimes have failed to show significant improvement in overall survival. Recent advances and in-depth understanding of the biology of melanoma have contributed in the development of new agents and to a change in the consideration of melanoma as one of the most therapy-resistant malignancies. Since the discovery of activating mutations in the BRAF oncogene, there has been remarkable progress in the development of targeted therapies for unresectable and metastatic melanoma, with unprecedentedly high response rates. Inactivation of immune regulatory checkpoints that limit T cell responses to melanoma has provided clinically validated targets for cancer immunotherapy, resulting in durable tumour responses. The combination of both approaches may result in additional benefits. Here we discuss current molecular targeted treatment options, immunotherapy and promising ongoing research to develop new strategies to treat melanoma.
authors.affiliation: Department of Medicine, Division of Hematology-Oncology, University of California Los Angeles (UCLA), CA, USA.
authors.forename: Blanca
authors.initials: B
authors.lastname: Homet
authors.forename: Antoni
authors.initials: A
authors.lastname: Ribas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D055808:Drug Discovery; D019008:Drug Resistance, Neoplasm; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D058990:Molecular Targeted Therapy; D010641:Phenotype; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors
keywords: BRAF mutant; immunotherapy; metastatic melanoma