title: miRNAs and resistance to EGFR-TKIs in EGFR-mutant non-small cell lung cancer: beyond 'traditional mechanisms' of resistance.
abstract: Epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have dramatically changed the prognosis of advanced non-small cell lung cancers (NSCLCs) that harbour specific EGFR activating mutations. However, the efficacy of an EGFR-TKI is limited by the onset of acquired resistance, usually within one year, in virtually all treated patients. Moreover, a small percentage of EGFR-mutant NSCLCs do not respond to an EGFR-TKI, thus displaying primary resistance. At the present time, several mechanisms of either primary and acquired resistance have been elucidated, and new drugs are currently under preclinical and clinical development in order to overcome resistance to treatment. Nevertheless, there still remains much to be thoroughly investigated, as so far research has mainly focused on the role of proteincoding genes involved in resistance to EGFR-TKIs. On the other hand, in line with the data underscoring the relevance of non-coding RNAs in the pathogenesis of lung cancer and modulation of response to systemic therapies, microRNAs (miRNAs) have been supposed to play an important role in resistance to EGFR-TKIs. The aim of this review is to briefly summarise the existing relationship between miRNAs and resistance to EGFR-TKIs, and also focusing on the possible clinical applications of miRNAs in reverting and overcoming such resistance.
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Biagio
authors.initials: B
authors.lastname: Ricciuti
authors.affiliation: Department of Experimental Medicine, University of Perugia, Perugia 06156, Italy.
authors.forename: Carmen
authors.initials: C
authors.lastname: Mecca
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Cenci
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Giulia Costanza
authors.initials: GC
authors.lastname: Leonardi
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Perrone
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Mencaroni
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Crinò
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Pathology, University of Perugia, Perugia 06156, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Grignani
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Baglivo
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Chiari
authors.affiliation: Department of Clinical and Experimental Medicine, Division of Pathology, University of Perugia, Perugia 06156, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Sidoni
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Paglialunga
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Currà
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Murano
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Minotti
authors.affiliation: Medical Oncology, Santa Maria della Misericordia Hospital, Azienda Ospedaliera di Perugia, Perugia 06156, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Metro
keywords: EGFR mutation; EGFR-TKI; NSCLC; miRNAs; resistance