title: Targeting the EGFR T790M mutation in non-small-cell lung cancer.
abstract: The presence of activating mutations of the epidermal growth factor receptor (EGFR) is predictive of response to first- and second-generation tyrosine kinase inhibitors (TKIs) in patients with advanced non-small-cell lung cancer (NSCLC). However, patients that initially respond to these drugs inexorably become resistant. The T790M mutation in the exon 20 of the EGFR is the main mechanism of resistance to EGFR TKIs occurring in over 50% of the cases. Third generation EGFR TKIs have been shown to be active in patients who progressed after TKI treatment and carry the T790M mutation. Areas covered: This review is focused on the implications of tumor heterogeneity for targeting the T790M in patients with NSCLC. Expert opinion: Pre-clinical and clinical data suggest that the T790M is heterogeneously expressed in tumors that become resistant to first- and second-generation EGFR TKIs. These findings have important implications for the molecular diagnostic of the T790M mutation. Indeed, the analysis of both the circulating free tumor DNA (ctDNA) isolated from plasma and the tumor tissue might provide complimentary information to identify patients carrying the T790M mutation. However, further studies are needed to better understand the influence of tumor heterogeneity on the activity of drugs targeting the T790M.
authors.affiliation: a Cell Biology and Biotherapy Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Normanno
authors.affiliation: a Cell Biology and Biotherapy Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Monica Rosaria
authors.initials: MR
authors.lastname: Maiello
authors.affiliation: a Cell Biology and Biotherapy Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Chicchinelli
authors.affiliation: b Laboratory of Pharmacogenomics , CROM-Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Iannaccone
authors.affiliation: b Laboratory of Pharmacogenomics , CROM-Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Esposito
authors.affiliation: c Surgical Pathology Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: De Cecio
authors.affiliation: a Cell Biology and Biotherapy Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Amelia
authors.initials: A
authors.lastname: D'alessio
authors.affiliation: a Cell Biology and Biotherapy Unit , Istituto Nazionale Tumori 'Fondazione G. Pascale'-IRCCS , Naples , Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: De Luca
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D009154:Mutation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D066246:ErbB Receptors
keywords: EGFR; T790M; resistance; tumor heterogeneity; tyrosine kinase inhibitors