Epigenetic code underlying EGFR-TKI resistance in non-small cell lung cancer: Elucidation of mechanisms and perspectives on therapeutic strategies

Abstract

Non-small-cell lung cancer (NSCLC) is the most common lung cancer subtype, and epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the core drugs used for its treatment. However, the emergence of drug resistance poses a significant challenge to their clinical efficacy. As a significant role-player in cancer development and maintenance, histone modifications, DNA methylation and noncoding RNA (ncRNA) changes have been proven to play a crucial part in driving EGFR-TKI resistance, which provides promising potential therapeutic targets and biomarkers for overcoming drug resistance. This review delves into the complex epigenetic mechanisms that cause EGFR-TKI resistance and emphasizes the potential of combined epigenetic therapies, aiming to provide better-targeted treatment options for NSCLC patients with NSCLC and drive innovative strategies to overcome the challenges of drug resistance.