Abstract
The discovery of epidermal growth factor receptor (EGFR) mutations in nonsmall cell lung cancer (NSCLC) has allowed the identification of a subset of patients whose tumours are exquisitely sensitive to EGFR tyrosine kinase inhibitors (TKIs). Despite the efficacy and superiority of EGFR TKIs over chemotherapy as first-line therapy, all patients will ultimately develop progressive disease, with a median of 9–13 months progression-free survival. A better understanding of the molecular mechanisms underlying resistance to EGFR TKIs can help design new drugs and therapeutic strategies to overcome resistance. This has been illustrated by the new generation TKIs that are effective on the T790M mutation, which is the most frequent mechanism of acquired resistance to EGFR TKIs. In this article, we will address the main molecular mechanisms of primary and acquired resistance to EGFR TKIs in EGFR-mutant NSCLC.
Footnotes
Previous articles in this series: No. 1: Girard N. Thymic epithelial tumours: from basic principles to individualised treatment strategies. Eur Respir Rev 2013; 22: 75–87. No. 2: Dooms C, Muylle I, Yserbyt J, et al. Endobronchial ultrasound in the management of nonsmall cell lung cancer. Eur Respir Rev 2013; 22: 169–177. No. 3: Lang-Lazdunski L. Surgery for nonsmall cell lung cancer. Eur Respir Rev 2013; 22: 382–404. No. 4: Bergot E, Levallet G, Campbell K, et al. Predictive biomarkers in patients with resected non-small cell lung cancer treated with perioperative chemotherapy. Eur Respir Rev 2013; 22: 565–576.
Provenance: Submitted article, peer reviewed.
Conflict of interest: Disclosures can be found alongside the online version of this article at err.ersjournals.com
- Received June 2, 2014.
- Accepted June 8, 2014.
- ©ERS 2014
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