CD39 and CD73: biological functions, diseases and therapy

Area of Science:

• Biochemistry
• Immunology
• Pharmacology

Background:

• CD39 and CD73 are ectonucleotidases crucial for purinergic signaling, regulating immune responses and homeostasis.
• These enzymes hydrolyze ATP/ADP and AMP to adenosine, influencing various physiological and pathological processes.
• CD39 and CD73 are increasingly recognized as significant therapeutic targets, especially in oncology.

Purpose of the Study:

• To provide a comprehensive review of current advancements in CD39 and CD73 research.
• To summarize the structural characteristics, enzymatic activities, and biological functions of CD39 and CD73.
• To discuss the therapeutic potential of CD39 and CD73 inhibitors across diverse disease states.

Main Methods:

• Literature review of preclinical and clinical studies on CD39 and CD73.
• Analysis of structural, functional, and distribution data for CD39 and CD73.
• Evaluation of various CD39 and CD73 inhibitors, including small molecules, antibodies, and combination therapies.

Main Results:

• CD39 and CD73 play critical roles in cancer, autoimmune, inflammatory, cardiovascular, infectious, and neurological disorders.
• Preclinical studies demonstrate anti-tumor efficacy of CD39 and CD73 inhibitors, primarily via adenosine-dependent mechanisms.
• Various inhibitor strategies, including small molecules, antibodies, and combination therapies, are under investigation.

Conclusions:

• CD39 and CD73 are promising therapeutic targets with broad applicability beyond cancer.
• Further research is needed to optimize inhibitor structures, delivery, and administration for improved selectivity and reduced off-target effects.
• Future efforts should focus on mechanistic exploration and rational drug design to broaden therapeutic potential.