Abstract
N6-methyladenosine (m6A) modification is a pivotal mechanism in RNA epigenetics, with profound implications for lung cancer (LC) biology. This review synthesizes current knowledge on m6A's multifaceted regulatory networks in non-small cell lung cancer (NSCLC), elucidating its roles in tumor proliferation, apoptosis, invasion, and metastasis. We further explore how m6A governs metabolic reprogramming-including glycolysis and ferroptosis-angiogenesis, and tumor microenvironment (TME) remodeling. Additionally, m6A-mediated modification of non-coding RNAs contributes to LC malignancy, underscoring its potential as a diagnostic and prognostic biomarker. These findings also offer novel strategies to overcome therapeutic resistance, a critical challenge in NSCLC treatment. Despite its promise, clinical translation of m6A-targeted interventions faces hurdles, such as the lack of standardized detection methods, the complexity of m6A-associated regulatory networks, and unresolved crosstalk with other RNA modifications. Future research should prioritize multi-omics approaches to resolve these challenges and advance m6A from mechanistic discovery toward clinical application. By addressing these gaps, m6A modulation may emerge as a transformative avenue in precision oncology.