title: [Systemic treatment of inoperable metastasized malignant melanoma].
abstract: BACKGROUND
  The medical therapy of inoperable malignant melanoma has changed dramatically over the last few years.
  
  
  OBJECTIVE
  The purpose of this article is to summarize the current state of systemic medical treatment of malignant melanoma.
  
  
  METHODS
  Clinical studies and guidelines in the therapy of malignant melanoma are reviewed.
  
  
  RESULTS
  Medical therapy of inoperable melanoma changed due to developments in immunotherapies (checkpoint inhibitors) and molecular-targeted therapies (BRAF and MEK inhibitors). Checkpoint inhibitors are antibodies administered as infusions every 2-3 weeks, blocking the checkpoints PD-1 or CTLA-4, thus, preventing downregulation of the immune system. BRAF and MEK inhibitors are small molecules, they are given orally and block a certain signaling pathway in tumor cells. The activation of this pathway has to be demonstrated by molecular analysis of tumor tissue first. This strategy is currently registered for 40-50 % of melanomas harboring a BRAF V600 mutation, while the combination of a BRAF plus MEK inhibitor has been proven more efficient than a BRAF inhibitor alone.
  
  
  CONCLUSIONS
  A fascinating development has started in the melanoma field due to immunotherapeutic and molecular-targeted treatment strategies. The continuation of this development needs further clinical and translational studies. This includes particular clinical studies with the new substances in the adjuvant situation, and sequences and combinations in the metastatic setting. Translational studies are needed to develop biomarkers for response and side effects.
authors.affiliation: Haut-Tumor-Zentrum Hannover (HTZH), Klinik für Dermatologie, Allergologie und Venerologie, Medizinische Hochschule Hannover (MHH), Carl-Neuberg Str. 1, 30625, Hannover, Deutschland. gutzmer.ralf@mh-hannover.de.
authors.forename: R
authors.initials: R
authors.lastname: Gutzmer
authors.affiliation: Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland.
authors.forename: R
authors.initials: R
authors.lastname: Rauschenberg
authors.affiliation: Klinik und Poliklinik für Dermatologie, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Deutschland.
authors.forename: F
authors.initials: F
authors.lastname: Meier
mesh_terms: D000284:Administration, Oral; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D019317:Evidence-Based Medicine; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D007262:Infusions, Intravenous; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D058990:Molecular Targeted Therapy / Q000379:methods*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents
keywords: BRAF inhibitors; Checkpoint inhibitors; Immunotherapy; MEK inhibitors; Molecular-targeted therapy