RNA Modifications in Tumor Microenvironment: A New Dimension for Cancer Treatment

ABSTRACT

RNA modifications are pivotal posttranscriptional gene expression regulators with profound functions in both physiological and pathological states, particularly during cancer initiation and progression. Within the complex tumor microenvironment (TME), these modifications orchestrate diverse mechanisms that significantly impact tumor growth, facilitate immune evasion, and drive therapeutic resistance. Recent advances have demonstrated their critical roles in shaping RNA metabolism and maintaining genome integrity, as well as modulating key stromal pathways such as immune responses, extracellular matrix remodeling, and vascular supply. Emerging evidence further suggests that RNA modifications dynamically regulate intercellular communication between tumor cells and surrounding stromal and immune cells within the TME. In this review, we provide a comprehensive overview of the mechanisms and functional roles of major RNA modifications, including adenosine, guanosine, and pseudouridine modifications. We discuss their regulatory roles in RNA metabolism and genome integrity, and examine their diverse functions within the TME, including immune regulation, tumor proliferation, extracellular matrix remodeling, and DNA damage response (DDR) pathways. Additionally, we highlight recent advances in therapeutic strategies targeting RNA‐modifying enzyme and discuss their potential for improving cancer treatment. Collectively, targeting RNA modification represents a promising strategy for overcoming cancer resistance and improving clinical treatment outcomes.