Rewriting the Fate of Cancer: Epigenetic and Epitranscriptomic Regulators in the Metastatic Cascade

Metastasis is the leading cause of cancer-related mortality, representing a highly coordinated, multistep process in which malignant cells gain the ability to invade, survive in the circulation, and establish secondary tumors at distant sites. While genetic mutations initiate oncogenesis, accumulating evidence shows that epigenetic and epitranscriptomic regulators, encompassing DNA methylation, RNA modifications, and noncoding RNAs (ncRNAs), reshape metastatic phenotypes. This review integrates current insights into these mechanisms and their crosstalk, with a primary focus on their methylation modification. Given their plasticity and potential reversibility, these regulators are attractive targets for therapeutic intervention. Defining the dynamic interplay between DNA and RNA modifications and ncRNAs provides a coherent framework for controlling metastasis and guides the development of precision epigenetic strategies and biomarkers. Future research that integrates multi-omics approaches and spatial transcriptomics will be essential for revealing the epigenetic and epitranscriptomic layers of the metastatic landscape.