m6A-Targeted Cancer Therapy: Molecular Targets, Inhibitors, and Nanodelivery Strategies

Abstract

Abstract m6A methylation modification, a widespread RNA post-transcriptional modification in eukaryotes, has been shown to play a crucial role in various biological processes, including gene expression regulation, cell proliferation and differentiation. By regulating RNA stability, translation, and degradation, m6A can influence the expression of oncogenic and tumor-suppressive transcripts and thereby contribute to cancer initiation and progression. In recent years, m6A-targeted therapy has emerged as a promising approach in cancer treatment, particularly with the development of m6A inhibitors and the integration of nano-delivery technologies, which have demonstrated significant therapeutic potential. This review summarizes recent advances in m6A-targeted cancer therapy, with emphasis on small-molecule inhibitors and RNA-based strategies targeting m6A regulators, and highlights their integration with nanocarriers, including lipid nanoparticles, polymeric nanoparticles, and extracellular vesicle-based systems, to improve drug stability, pharmacokinetic properties, tumor accumulation, and therapeutic selectivity. This integrated perspective highlights the emerging role of nanodelivery in advancing m6A-targeted cancer therapy and provides a framework for understanding its therapeutic potential. Despite these advances and promising preclinical evidence, the clinical translation of m6A-targeted therapies remains limited, with challenges related to drug specificity, delivery optimization, and the complexity of m6A regulatory networks. Finally, the article envisions future research directions, emphasizing the integration of interdisciplinary technologies, and predicts the broad prospects of m6A-targeted therapy in precision cancer treatment.