Emerging Role of Noncoding RNAs in EGFR TKI-Resistant Lung Cancer.

Abstract

Simple SummaryThe introduction of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment of lung cancer. Nevertheless, TKI resistance impedes therapeutic efficacy and its underlying mechanisms remain unclear. This review summarizes the potential mechanisms of noncoding RNAs (ncRNAs) in EGFR TKI-resistant lung cancer and their clinical applications. Moreover, we highlight the bottlenecks that urgently need to be addressed to promote the clinical application of ncRNAs.Lung cancer accounts for the majority of malignancy-related mortalities worldwide. The introduction of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has revolutionized the treatment and significantly improved the overall survival (OS) of lung cancer. Nevertheless, almost all EGFR-mutant patients invariably acquire TKI resistance. Accumulating evidence has indicated that noncoding RNAs (ncRNAs), such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), have a central role in the tumorigenesis and progression of lung cancer by regulating crucial signaling pathways, providing a new approach for exploring the underlying mechanisms of EGFR-TKI resistance. Therefore, this review comprehensively describes the dysregulation of ncRNAs in EGFR TKI-resistant lung cancer and its underlying mechanisms. We also underscore the clinical application of ncRNAs as prognostic, predictive and therapeutic biomarkers for EGFR TKI-resistant lung cancer. Furthermore, the barriers that need to be overcome to translate the basic findings of ncRNAs into clinical practice are discussed.