title: Current therapeutic leads for the treatment of melanoma: targeted immunotherapy in the post-genomic era.
abstract: Metastatic melanoma has a poor prognosis and until today most therapeutic approaches are ineffective. Advances in molecular pathology and genome analysis technologies have led to the identification of genetic events and immune regulatory checkpoints that provide novel targets for pharmaceutical intervention in melanoma. Development of selective mitogen-activated kinase (MAPK) pathway inhibitors was the first major achievement coming from genetic studies that identified a constitutively active MAP kinase pathway and BRAF activating mutations in melanoma. At the same time, the manipulation of immune system checkpoints through monoclonal antibodies changed clinical practice and led to further improvement of patient outcomes. In an effort to further develop melanoma targeted therapies that depend on the genetic profile of a given patient, high-throughput genome wide approaches (next-generation sequencing [NGS], gene arrays, etc) have been employed for the characterization of genetic alterations in the patient's tumor. In the near future, the combined information from the genetic and immune background of an individual will provide the basis for a personalized, highly targeted approach in the treatment of melanoma.
authors.forename: Anastasios D
authors.initials: AD
authors.lastname: Papanastasiou
authors.forename: Chaido
authors.initials: C
authors.lastname: Sirinian
authors.forename: Haralabos P
authors.initials: HP
authors.lastname: Kalofonos
authors.affiliation: Department of Pathology, Patras General Hospital, and Clinical and Molecular Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, Patras, Greece. apapanasta@gmail.com.
authors.forename: Maria
authors.initials: M
authors.lastname: Repanti
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000276:immunology; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007167:Immunotherapy; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D020930:MAP Kinase Kinase Kinases