title: New therapeutic options in systemic treatment of advanced cutaneous melanoma.
abstract: BACKGROUND
  For many years systemic treatment of advanced/metastatic melanoma has been based on chemotherapy or immunotherapy. However, even very toxic regimens (e.g., polychemotherapy, bio-chemotherapy or immunotherapy with HD-IL-2) despite increased response rates as compared with standard dacarbazine monotherapy have not improved patients' outcomes. Over the last two decades, a huge effort, made in order to determine the molecular and immunological mechanisms responsible for biology of melanoma led to development of novel targeted agents.
  
  
  METHODS
  The aim of this article is to summarize data on novel targeted agents used for treatment of metastatic melanoma. The authors searched PubMed, EMBASE and abstracts from ASCO, ESMO, AACR congresses for Phase II/III clinical studies evaluating novel immunomodulating agents and kinase inhibitors in melanoma patients.
  
  
  CONCLUSIONS
  Elucidation of the crucial role of MAPK pathway and BRAF kinase mutations in particular has led to development of specific small molecule kinase inhibitors (vemurafenib, dabrafenib, trametinib), and new insight into molecular mechanisms responsible for immune response and tolerance resulted in development of immunomodulatory agents (ipilimumab, anti-PD1, anti-PD-L1). The introduction of novel drugs has changed the natural history of melanoma. However, it has also generated new clinical challenges that have to be resolved as soon as possible.
authors.affiliation: University of Medical Sciences, Department of Dermatology, Poznan, Poland.
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Mackiewicz-Wysocka
authors.forename: Jakub
authors.initials: J
authors.lastname: Zolnierek
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Wysocki
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D002986:Clinical Trials as Topic; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D009361:Neoplasm Invasiveness; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000276:immunology; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000276:immunology / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D004791:Enzyme Inhibitors; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor