CD39 and CD73: biological functions, diseases and therapy

作者：J. Shen, Bin Liao, Li Gong, Sha Li, Juan Zhao, Huiyao Yang, Yi Gong, Yongsheng Li · 发表于：Molecular Biomedicine · 年份：2025 · DOI：10.1186/s43556-025-00345-9 · 被引用次数：27 · 研究领域：Adenosine and Purinergic Signaling、Cardiac Ischemia and Reperfusion、Peptidase Inhibition and Analysis

Cluster of differentiation 39 (CD39) and CD73 are ectonucleotidases that play pivotal roles in purinergic signaling. CD39 catalyzes the hydrolysis of adenosine triphosphate (ATP) to adenosine diphosphate (ADP) and subsequently to adenosine monophosphate (AMP), while CD73 further catalyzes the hydrolysis of AMP to adenosine. These ectonucleotidases are expressed across diverse cell types and exhibit pleiotropic functions in immune regulation, physiological homeostasis, and disease pathogenesis. Recent preclinical studies have increasingly identified CD39 and CD73 as promising therapeutic targets in various disease states, particularly in cancer. This review provides a comprehensive summary of the current advancements in CD39 and CD73 research, emphasizing their structural characteristics, distribution, enzymatic and non-enzymatic activities, as well as their biological functions. We discuss the involvement of CD39 and CD73 in multiple disease states, including cancer, autoimmune disorders, inflammatory diseases, cardiovascular disorders, infectious diseases, and neurological disorders. Furthermore, we present existing preclinical and clinical research on reported CD39 and CD73 inhibitors, which include small-molecule inhibitors, antibodies, advanced delivery systems, and combinations with adenosine receptor antagonists, targeted therapy, immunotherapy, and chemotherapy, thereby providing a foundation for future investigations. The anti-tumor efficacy of these inhibitors, obser...