Exploring the role of RNA modifications in tumor metastasis and therapy resistance: molecular mechanisms and clinical implications

RNA modifications represent a pivotal layer of epigenetic regulation, fine‑tuning gene expression post‑transcriptionally and maintaining cellular homeostasis. Recent methodological advances have increasingly highlighted their roles in tumor initiation and progression. Tumor metastasis and therapy resistance are major contributors to cancer‑related mortality and clinical treatment failure, underpinned by highly complex and dynamically plastic molecular mechanisms. Growing evidence demonstrates that RNA modifications are deeply involved in these processes by regulating tumor‑cell phenotypic plasticity, remodeling the tumor microenvironment, and modulating therapeutic responses. Despite increasing recognition of RNA modifications in cancer, a comprehensive understanding of how they regulate metastasis and therapeutic resistance remains lacking. This review systematically outlines major RNA modification types and their key regulatory factors, with a particular emphasis on their molecular mechanisms in tumor metastasis and therapy resistance. Furthermore, it delineates core signaling pathways and downstream effectors linked to RNA modifications, and comprehensively discusses their functional landscapes across diverse cancer types. By doing so, it deepens the understanding of post‑transcriptional regulatory networks driving metastasis and resistance, and provides a theoretical foundation for identifying RNA modification‑based biomarkers and developing precision therapeutic strategies.