RNA modifications in cancer: from biological insights to therapeutic targets

RNA modifications represent an essential regulatory layer of gene expression and have profound implications for cellular homeostasis and human diseases. Advances in high-throughput sequencing technologies have revealed that modifications such as N 6 -methyladenosine (m 6 A) and pseudouridine (Ψ) influence cellular processes such as gene transcription, pre-mRNA processing, mRNA stability, and translation. This review begins with a historical overview of the field, highlighting key discoveries and technological advances that gave rise to epitranscriptomics as a discipline. The biological functions of RNA modifications are then examined, with emphasis on their contributions to cancer development. Recent efforts in targeting RNA modification are summarized, including small-molecule inhibitors targeting effector proteins of RNA modification. Several of these inhibitors have demonstrated efficacy in preclinical cancer models, underscoring the therapeutic potential of modulating the epitranscriptome. As research in this area expands, RNA modifications are increasingly recognized as both pivotal drivers of tumorigenesis and promising targets for cancer therapy. • RNA modifications add a key regulatory layer to gene expression. • Dysregulated m 6 A and Ψ drive tumor growth, metastasis and immune evasion. • Small-molecule inhibitors of RNA modification effectors show antitumoral efficacy. • Targeting the epitranscriptome offers novel strategies against cancer.