title: The role of phenotypic plasticity in the escape of cancer cells from targeted therapy.
abstract: Targeted therapy has proven to be beneficial at producing significant responses in patients with a wide variety of cancers. Despite initially impressive responses, most individuals ultimately fail these therapies and show signs of drug resistance. Very few patients are ever cured. Emerging evidence suggests that treatment of cancer cells with kinase inhibitors leads a minor population of cells to undergo a phenotypic switch to a more embryonic-like state. The adoption of this state, which is analogous to an epithelial-to-mesenchymal transition, is associated with drug resistance and increased tumor aggressiveness. In this commentary we will provide a comprehensive analysis of the mechanisms that underlie the embryonic reversion that occurs on targeted cancer therapy and will review potential novel therapeutic strategies designed to eradicate the escaping cells.
authors.affiliation: The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Emmons
authors.affiliation: The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA; The Department of Clinical and Toxicological Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Faião-Flores
authors.affiliation: The Department of Tumor Biology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA; The Department of Cutaneous Oncology, The Moffitt Cancer Center & Research Institute, 12902 Magnolia Drive, Tampa, FL, USA. Electronic address: keiran.smalley@moffitt.org.
authors.forename: Keiran S M
authors.initials: KSM
authors.lastname: Smalley
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016503:Drug Delivery Systems; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D016896:Treatment Outcome
keywords: BRAF; EGFR; EMT; Lung cancer; Melanoma