Arginine methylation in cancer: mechanisms and therapeutic implications

Arginine methylation is a critical post-translational modification that modulates protein stability, enzymatic activity, and subcellular localization, thereby shaping cell fate decisions and maintaining cellular homeostasis. As the principal enzymes catalyzing this modification, protein arginine methyltransferases (PRMTs) participate in key biological processes, including transcriptional and post-transcriptional regulation as well as signal transduction. Dysregulated PRMT activity has been increasingly linked to tumor initiation, progression, and therapeutic resistance. This review summarizes PRMT classification, structural and functional characteristics, and upstream regulatory mechanisms, offering a framework for understanding their diverse roles in cancer biology and therapeutic relevance. We further discuss the mechanistic contributions of PRMTs to multiple cancer hallmarks and highlight recent advances in the development of PRMT inhibitors. Finally, we examine current strategies for clinical translation, with particular emphasis on combination approaches involving chemotherapy, targeted therapy, and immunotherapy, thereby offering a foundation for advancing PRMT-targeted precision oncology.