Evidence map›Paper›PMID 41889017›Full record

ReviewNucleosides, nucleotides & nucleic acids2026

Deoxycytidine kinase inhibition: Rewiring tumor nucleotide metabolism for therapeutic gain.

Peter M Clark, Curtis B Thompson, Kenneth A Schultz

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Nucleosides, nucleotides & nucleic acids, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

Peter M ClarkDepartment of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, California, USA.
Curtis B ThompsonTrethera Corporation, Los Angeles, California, USA.
Kenneth A SchultzTrethera Corporation, Los Angeles, California, USA.

Funding

Development of a novel, targeted small molecule inhibitor of the nucleoside salvage pathway through combinatorial murine studies to enable further clinical advancement in prostate tumorsR44CA302066 · NCI · TRETHERA CORPORATION · PI Kenneth Schultz · 2025 to 2026
$2.3M
Development of a Novel, Targeted Small Molecule Inhibitor of the Nucleotide Salvage Pathway to Treat Underserved Tumor TypesR44CA281485 · NCI · TRETHERA CORPORATION · PI SCHULTZ, KENNETH · 2023 to 2024
$2.0M
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 cancerR44CA306475 · NCI · TRETHERA CORPORATION · PI SCHULTZ, KENNETH · 2025 to 2025
$407k
NCI NIH HHS R44 CA281485NCI NIH HHS R44 CA302066NCI NIH HHS R44 CA306475
6 · The paper itself

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.

Indexed as

Antineoplastic AgentsDeoxycytidine KinaseNeoplasmsNucleotidesAnimalsHumansAntineoplastic AgentsDeoxycytidine KinaseNucleotidescancerDeoxycytidine kinasedeoxyribonucleoside salvagemetabolic vulnerability

Identifiers

PMID41889017
PMCPMC13078960

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.