title: Phenotypic tumour cell plasticity as a resistance mechanism and therapeutic target in melanoma.
abstract: Despite the recent success of MAPK and immune checkpoint inhibitors in advanced melanoma, intrinsic and acquired resistance mechanisms determine the efficacy of these therapeutic approaches. Therapy resistance in melanoma is not solely driven by genetic evolution, but also by epigenetically driven adaptive plasticity. Melanoma cells are shifting between different transcriptional programs, cell cycle states and differentiation phenotypes reflecting a highly dynamic potential to adapt to various exogenous stressors including immune attack or cancer therapies. This review will focus on the dynamic interconversion and overlap between different melanoma cell phenotypes in the context of therapy resistance and a dynamically changing multicellular microenvironment.
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany. Electronic address: alexander.roesch@uk-essen.de.
authors.forename: Alexander
authors.initials: A
authors.lastname: Roesch
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Paschen
authors.affiliation: Department of Dermatology and Allergy, University of Bonn, 53127 Bonn, Germany.
authors.forename: Jenny
authors.initials: J
authors.lastname: Landsberg
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Iris
authors.initials: I
authors.lastname: Helfrich
authors.affiliation: German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany; Translational Skin Cancer Research, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.
authors.forename: Jürgen C
authors.initials: JC
authors.lastname: Becker
authors.affiliation: Department of Dermatology, Venereology, and Allergology, University Hospital Essen, University of Duisburg-Essen, 45122 Essen, Germany; German Cancer Consortium (DKTK), Partner Site Essen/Düsseldorf, West German Cancer Center, University of Duisburg-Essen, 45122 Essen, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D019008:Drug Resistance, Neoplasm / Q000276:immunology / Q000502:physiology*; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology / Q000502:physiology; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy / Q000379:methods*; D014411:Neoplastic Stem Cells / Q000276:immunology / Q000502:physiology; D010641:Phenotype; D019139:Tumor Escape / Q000276:immunology / Q000502:physiology; D059016:Tumor Microenvironment / Q000276:immunology / Q000502:physiology
keywords: Melanoma; Therapy resistance; Tumour heterogeneity; Tumour plasticity