title: The role of epithelial to mesenchymal transition in resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer.
abstract: Inhibition of the epidermal growth factor receptor (EGFR) is an important strategy when treating non-small cell lung cancer (NSCLC) patients. However, intrinsic resistance or development of resistance during the course of treatment constitutes a major challenge. The knowledge on EGFR-directed tyrosine kinase inhibitors (TKIs) and their biological effect keeps increasing. Within the group of patients with EGFR mutations some benefit to a much higher degree than others, and for patients lacking EGFR mutations a subset experience an effect. Up to 70% of patients with EGFR mutations and 10-20% of patients without EGFR mutations initially respond to the EGFR-TKI erlotinib, but there is a severe absence of good prognostic markers. Despite initial effect, all patients acquire resistance to EGFR-TKIs. Multiple mechanisms have implications in resistance development, but much is still to be explored. Epithelial to mesenchymal transition (EMT) is a transcriptionally regulated phenotypic shift rendering cells more invasive and migratory. Within the EMT process lays a need for external or internal stimuli to give rise to changes in central signaling pathways. Expression of mesenchymal markers correlates to a bad prognosis and an inferior response to EGFR-TKIs in NSCLC due to the contribution to a resistant phenotype. A deeper understanding of the role of EMT in NSCLC and especially in EGFR-TKI resistance-development constitute one opportunity to improve the benefit of TKI treatment for the individual patient. Many scientific studies have linked the EMT process to EGFR-TKI resistance in NSCLC and our aim is to review the role of EMT in both intrinsic and acquired resistance to EGFR-TKIs.
authors.affiliation: 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark ; 2 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kristine Raaby
authors.initials: KR
authors.lastname: Jakobsen
authors.affiliation: 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark ; 2 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Demuth
authors.affiliation: 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark ; 2 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Boe Sandahl
authors.initials: BS
authors.lastname: Sorensen
authors.affiliation: 1 Department of Biomedicine, Aarhus University, Aarhus, Denmark ; 2 Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anders Lade
authors.initials: AL
authors.lastname: Nielsen
keywords: Epidermal growth factor receptor (EGFR); epithelial to mesenchymal transition (EMT); non-small cell lung cancer (NSCLC); tyrosine kinase inhibitor (TKI)