Molecular Mechanism of EGFR-TKI Resistance in -Mutated Non-Small Cell Lung Cancer: Application to Biological Diagnostic and Monitoring.
Fiche publication
Date publication
septembre 2021
Journal
Cancers
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BEAU-FALLER Michèle, Dr GUERIN Eric, Dr PENCREACH Erwan, Dr VALLAT Laurent, Dr REITA Damien, Pr MASCAUX Céline
Tous les auteurs :
Reita D, Pabst L, Pencreach E, Guérin E, Dano L, Rimelen V, Voegeli AC, Vallat L, Mascaux C, Beau-Faller M
Lien Pubmed
Résumé
Non-small cell lung cancer (NSCLC) is the most common cancer in the world. Activating epidermal growth factor receptor () gene mutations are a positive predictive factor for EGFR tyrosine kinase inhibitors (TKIs). For common mutations (Del19, L858R), the standard first-line treatment is actually third-generation TKI, osimertinib. In the case of first-line treatment by first (erlotinib, gefitinib)- or second-generation (afatinib) TKIs, osimertinib is approved in second-line treatment for patients with T790M mutation. Despite the excellent disease control results with EGFR TKIs, acquired resistance inevitably occurs and remains a biological challenge. This leads to the discovery of novel biomarkers and possible drug targets, which vary among the generation/line of EGFR TKIs. Besides second/third mutations, alternative mechanisms could be involved, such as gene amplification or gene fusion, which could be detected by different molecular techniques on different types of biological samples. Histological transformation is another mechanism of resistance with some biological predictive factors that needs tumor biopsy. The place of liquid biopsy also depends on the generation/line of EGFR TKIs and should be a good candidate for molecular monitoring. This article is based on the literature and proposes actual and future directions in clinical and translational research.
Mots clés
EGFR mutations, cell-free DNA, molecular analysis, next-generation sequencing, non-small cell lung cancer, resistance mechanisms, tyrosine kinase inhibitors
Référence
Cancers (Basel). 2021 Sep 30;13(19):