Characterising acquired resistance to erlotinib in non-small cell lung cancer patients. (3rd October 2019)

• Record Type: Journal Article
• Authors: Karachaliou, Niki; Codony-Servat, Jordi; Bracht, Jillian Wilhelmina Paulina; Ito, Masaoki; Filipska, Martyna; Pedraz, Carlos; Chaib, Imane; Bertran-Alamillo, Jordi; Cardona, Andres Felipe; Molina, Miguel Angel; Rosell, Rafael
• Is Part Of: Expert review of respiratory medicine. Volume 13:Number 10(2019)
• Page Start: 1019
• Page End: 1028
• Publication Date: 2019-10-03
• Subjects: Erlotinib -- resistance -- combinatory therapies; Respiratory organs -- Diseases -- Periodicals; Respiratory organs -- Diseases -- Treatment -- Periodicals; 616.2005
• DOI: 10.1080/17476348.2019.1656068
• Languages: English
• ISSNs: 1747-6348

Abstract

ABSTRACT: Introduction : The therapy of patients with lung adenocarcinoma has significantly changed after the discovery of epidermal growth factor receptor (EGFR) mutations. EGFR mutations occur in 10–15% of Caucasian lung cancer patients and are associated with favorable outcome to orally administered EGFR tyrosine kinase inhibitors (TKIs), like erlotinib. However, as soon as the tumor cells are under the pressure of the specific inhibitor, compensatory signaling pathways are activated and resistance emerges. Areas covered : In this review we will focus on the mechanisms of resistance to the first-generation EGFR TKI, erlotinib, and will mainly summarize the findings throughout the last 10 years in the field of EGFR-mutant lung cancer. Expert opinion : Widespread research has been performed and several mechanisms of resistance to EGFR TKIs, especially first- and second-generation, have been identified. Still, no adequate combinatory therapies have received regulatory approval for the treatment of EGFR-mutant patients at the time of resistance. The third-generation EGFR TKI, osimertinib has been approved for patients whose tumor has become resistant through the secondary T790M resistant EGFR mutation. The identification of the mechanisms of resistance and the application of the adequate therapy to each patient is still an unmet need.