title: Therapy of metastatic malignant melanoma: on the way to individualized disease control.
abstract: After decades of therapeutic frustration, the identification of some fundamental molecular drivers finally set the stage for the development of targeted therapies of metastatic malignant melanoma. With the invention of B-RAF inhibitors, targeting the mutated and activated B-RAF molecule in the MAP kinase cascade, objective responses can be achieved in about 50% of those cases harbouring this specific mutation. However, the effects are often short-lived with an average duration of 5-6 months. Hence, the challenge is to make such remissions stable and prevent secondary resistance. Currently, both the combination of targeted drugs and the invention of effective immunomodulating antibodies, e.g., anti-CTLA4 as well as anti-PD1, hold great promise to proceed on the way to individualized disease control, if not, as a remote aim, cure of this deadly cancer. Finally, progress has been made in identification and targeting of cancer stem cells, which seem to exhibit a kind of primary drug resistance and create the source of relapses and growth of clones with acquired secondary drug resistance.
authors.forename: Thomas
authors.initials: T
authors.lastname: Vogt
mesh_terms: D000906:Antibodies / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D060908:CTLA-4 Antigen / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000556:secondary; D009154:Mutation; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000473:pathology; D057285:Precision Medicine; D061026:Programmed Cell Death 1 Receptor / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D012074:Remission Induction; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000473:pathology; D000096142:Cutaneous Malignant Melanoma
chemical_list: D000906:Antibodies; D000970:Antineoplastic Agents; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf