title: Phenotype switching: tumor cell plasticity as a resistance mechanism and target for therapy.
abstract: Mutations in BRAF are present in the majority of patients with melanoma, rendering these tumors sensitive to targeted therapy with BRAF and MEK inhibitors. Unfortunately, resistance almost invariably develops. Recently, a phenomenon called "phenotype switching" has been identified as an escape route. By switching from a proliferative to an invasive state, melanoma cells can acquire resistance to these targeted therapeutics. Interestingly, phenotype switching bears a striking resemblance to the epithelial-to-mesenchymal-like transition that has been described to occur in cancer stem cells in other tumor types. We propose that these changes are manifestations of one and the same underlying feature, namely a dynamic and reversible phenotypic tumor cell plasticity that renders a proportion of cells both more invasive and resistant to therapy. At the same time, the specific characteristics of these tumor cell populations offer potential for being explored as target for therapeutic intervention.
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Kristel
authors.initials: K
authors.lastname: Kemper
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Pauline L
authors.initials: PL
authors.lastname: de Goeje
authors.affiliation: Division of Molecular Oncology, Netherlands Cancer Institute, Amsterdam, the Netherlands.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Peeper
authors.affiliation: Section of Molecular Cytology, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, the Netherlands. r.vanamerongen@uva.nl.
authors.forename: Renée
authors.initials: R
authors.lastname: van Amerongen
mesh_terms: D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D047428:Protein Kinase Inhibitors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf