Year: 2026
Type: article
Abstract: Deoxycytidine kinase (dCK) is the rate-limiting enzyme of the deoxyribonucleoside salvage pathway, phosphorylating deoxyadenosine, deoxycytidine, and deoxyguanosine to sustain intracellular deoxyribonucleoside triphosphate (dNTP) pools. Replication stress and DNA damage enhance dCK activity, creating tumor dependence on salvage-mediated dNTP supply for DNA repair and survival. Genetic contexts such as BRCA2 loss and mutant p53 further heighten this vulnerability. This review synthesizes mechanistic evidence linking dCK to stress-adaptive nucleotide metabolism, summarizes progress in small-molecule dCK inhibitor development, and highlights dCK inhibitor TRE-515 as the first clinically tested agent, alongside plasma nucleoside profiling and PET imaging as translational pharmacodynamic biomarkers.
Institution: University of California System
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Awards: Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleotide Salvage Pathway to Treat Underserved Tumor Types, G9000372942, G9000375339, G9000380586, Development of a novel, targeted small molecule inhibitor of the nucleoside salvage pathway through murine studies to enable further clinical advancement in non-small-cell lung cancer, Development of a novel, targeted small molecule inhibitor of the nucleoside salvage pathway through combinatorial murine studies to enable further clinical advancement in prostate tumors
OpenAlex ID: W7141488343