Journal of cancer research and therapeutics
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Lung cancer continues to be a major health problem and the most common cancer-related mortality worldwide with about 80%-85% patients suffering from nonsmall cell lung cancer (NSCLC). More than 80% of NSCLC cases are often diagnosed as advanced stage and harbor epidermal growth factor receptor (EGFR) activating mutation. Although great success in initial response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs) are found in EGFR-mutant NSCLC patients, acquired resistance usually occurs on the continuous treatment. ⋯ Increasing evidence has proven that non-coding RNA including long noncoding RNAs and microRNAs or new EGFR mutation is involved in acquired resistance. Preclinical and clinical Phase 1-3 evidence on combination drug therapy or new generation inhibitors with different tumor-targeting approaches have made those strategies the promising options for EGFR-TKI-resistant NSCLC therapy. This review aims to get deep insight into providing a state-of-the-art overview of the recent advances in the mechanisms of acquired resistance and new strategies for targeted cancer therapy in EGFR-TKI-resistant NSCLC.