Nucleotide-metabolizing enzymes

Nucleotide-metabolizing enzymes are a diverse group of proteins responsible for the synthesis, interconversion, and degradation of nucleotides, which function as both genetic building blocks and extracellular signaling molecules (UniProt, 2024, https://www.uniprot.org/). In the context of oncology, the most prominent members are ectonucleotidases such as CD39 and CD73, which form a catalytic pathway that converts pro-inflammatory extracellular ATP into immunosuppressive adenosine (Nature Reviews Cancer, 2019, https://doi.org/10.1038/s41568-019-0143-5). This metabolic shift is a key mechanism of immune evasion, as adenosine binds to receptors on immune cells to inhibit their anti-tumor activity (Frontiers in Pharmacology, 2020, https://doi.org/10.3389/fphar.2020.01017). Beyond the extracellular space, intracellular enzymes like adenosine deaminase (ADA) and various kinases are essential for maintaining the nucleotide pools required for DNA repair and cellular energy homeostasis (PubMed, 2021, https://pubmed.ncbi.nlm.nih.gov/33806105/). Drugs targeting these enzymes include antimetabolites for chemotherapy and monoclonal antibodies designed to restore immune function in the tumor microenvironment (Journal for ImmunoTherapy of Cancer, 2021, https://doi.org/10.1136/jitc-2021-002493). Because this term describes a broad functional class rather than a single protein, therapeutic applications vary widely depending on the specific enzyme targeted.

Other names

EctonucleotidasesPurinergic signaling enzymesNucleotide-processing enzymesNucleotide hydrolases

Inhibition of the enzymatic conversion of extracellular ATP to adenosine to reverse immunosuppression, or inhibition of intracellular nucleotide synthesis to prevent cell division.