Epitranscriptomic control of cancer hallmarks: Functions, mechanisms, and therapeutics of RNA modifications.

The epitranscriptome, comprising over 170 distinct RNA modifications, represents a dynamic and multifaceted layer of gene regulation. These chemical marks such as N6-methyladenosine (m6A), 5-methylcytosine (m5C), and pseudouridine (Ψ) modulate RNA processing, localization, stability, and translation, shaping cell identity and stress responses. In cancer, RNA modifications integrate with oncogenic signaling networks to influence cancer cell proliferation, metabolism, immune evasion, stemness, and therapeutic resistance. Recent advances in detection technologies, functional perturbation tools, and spatial profiling have accelerated our understanding of the epitranscriptome's roles and the underlying mechanisms in malignancies. In this review, we provide a mechanistic framework connecting RNA modifications and regulators to the hallmarks of cancer. We highlight emerging insights into the interface between epitranscriptomic regulators and canonical cancer pathways and evaluate their potential as biomarkers and therapeutic targets. Together, these findings underscore RNA modification as a pivotal regulatory axis in cancer biology and a promising frontier for translational intervention.