Purine metabolism in tumorigenesis and its clinical implications

Metabolic reprogramming constitutes a hallmark of malignant neoplasms. Purine metabolism emerges as a pivotal regulator in cellular metabolic networks through multiple mechanisms, including dysregulation of de novo biosynthesis/salvage pathway coordination, adenosine-mediated immunosuppressive microenvironment formation, and collective contributions to tumorigenesis and malignant progression. During metastatic progression, purine metabolism reinforces tumor cell plasticity through mitochondrial energy regulation and modulation of cell cycle checkpoints (eg, G1/S transition). These mechanistic revelations have positioned purine metabolism-targeting strategies as promising oncotherapeutic candidates. This review methodically analyzes (1) purine metabolic pathways and their regulatory dynamics, (2) adenosine-mediated pathophysiological interactions, and (3) the synergistic impacts of these pathways in malignant transformation. We propose a unified mechanistic framework that clarifies oncogenic purine metabolic rewiring while evaluating translational potential through three clinical dimensions: pathogenesis elucidation, diagnostic biomarker discovery, and targeted therapeutic development. This comprehensive synthesis aims to advance precision oncology through mechanistic insights and therapeutic innovation.