Long non-coding RNAs in non-small cell lung cancer: implications for EGFR-TKI resistance

Non-small cell lung cancer (NSCLC) is one of the most common types of malignant tumors as well as the leading cause of cancer-related deaths in the world. The application of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) has dramatically improved the prognosis of NSCLC patients who harbor EGFR mutations. However, despite an excellent initial response, NSCLC inevitably becomes resistant to EGFR-TKIs, leading to irreversible disease progression. Hence, it is of great significance to shed light on the molecular mechanisms underlying the EGFR-TKI resistance in NSCLC. Long non-coding RNAs (lncRNAs) are critical gene modulators that are able to act as oncogenes or tumor suppressors that modulate tumorigenesis, invasion, and metastasis. Recently, extensive evidence demonstrates that lncRNAs also have a significant function in modulating EGFR-TKI resistance in NSCLC. In this review, we present a comprehensive summary of the lncRNAs involved in EGFR-TKI resistance in NSCLC and focus on their detailed mechanisms of action, including activation of alternative bypass signaling pathways, phenotypic transformation, intercellular communication in the tumor microenvironment, competing endogenous RNAs (ceRNAs) networks, and epigenetic modifications. In addition, we briefly discuss the limitations and the clinical implications of current lncRNAs research in this field.