The m⁶A modification in cancer: roles, implications, and its potential in therapy

N⁶-methyladenosine (m⁶A) serves as the dominant epitranscriptomic mark within eukaryotic mRNA transcripts, exerting pivotal regulatory functions in modulating mRNA structural integrity, translational efficiency, and splicing, thereby influencing gene expression patterns in cancer cells. m⁶A modification is recognized as a principal epigenetic determinant in driving malignant progression and fostering therapeutic resistance, making it crucial for advancing precision oncology. This review begins with a brief introduction to m⁶A modification, with a particular focus on its dynamic variability in distinct malignancies and clinical staging scenarios. Moreover, we underscore the critical functions of m⁶A methylation in cancer biology, including cancer-related molecular networks, cancer hallmarks, cancer stem cells, and the tumor microenvironment. We further outline the implications of m⁶A dysregulation in cancer, emphasizing the diagnostic potential of m⁶A regulators, the prognostic value of m⁶A, and the role of m⁶A in treatment resistance. Additionally, we analyze the potential of m⁶A modification in cancer therapy, encompassing the use of m⁶A inhibitors, combinations with existing cancer therapies, and personalized medicine approaches. Finally, we dissect the current limitations and future directions in m⁶A modification research, directing resources toward the development of high-throughput platforms for the dynamic monitoring of m⁶A modification in living systems. Overall, this review reinforces the central significance of m⁶A modification in cancer biology, emphasizing its transformative capacity to reshape cancer diagnostic paradigms and therapeutic intervention strategies.