ReviewNature reviews. Clinical oncology2014
Standing the test of time: targeting thymidylate biosynthesis in cancer therapy.
Review in Nature reviews. Clinical oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers.
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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.
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.
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Who cites it
212 citing papers in PubMed, 388 citations in OpenAlex.
- ECOG-ACRIN E6293: Phase II Study of Raltitrexed in Advanced Colorectal Cancer.The oncologist · 2026Trial
- Features of durable response and treatment efficacy for capecitabine monotherapy in advanced breast cancer: real-world evidence from a large single-centre cohort.Journal of cancer research and clinical oncology · 2021Trial
- Relationship between folate concentration and expression of folate-associated genes in tissue and plasma after intraoperative administration of leucovorin in patients with colorectal cancer.Cancer chemotherapy and pharmacology · 2018Trial
- Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine-Induced Hand-Foot Syndrome: A Randomized Clinical Trial.JAMA oncology · 2017Trial
- A phase 1 study of the pharmacokinetics of nucleoside analog trifluridine and thymidine phosphorylase inhibitor tipiracil (components of TAS-102) vs trifluridine alone.Investigational new drugs · 2017Trial
- Dietary supplement use throughout the colorectal cancer disease trajectory: a prospective cohort study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Article
- VCP-Regulated LMF2 Stabilizes the Cholesterol Biosynthesis Enzyme HMGCS1 to Drive Cancer Progression and Confer Capecitabine Resistance in Triple-Negative Breast Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ribonucleotides Amplify Mitochondrial DNA-Driven cGAS-STING Activation via FdUMP-ribonucleotide Hybrid Particles to Potentiate Chemoimmunotherapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Fusion-positive rhabdomyosarcoma oncofusions share a common interactome.Nature communications · 2026Article
- Metronomic Capecitabine Triggers Ferroptosis in Hepatocellular Carcinoma Cells Through Inhibition of TYMS.Cancer medicine · 2026Article
- Chemotherapy-Induced Oral Mucosal Injury Is Defined by p53 Activation, Cell Cycle Arrest and Diverse Epithelial Progenitor Dynamics.bioRxiv : the preprint server for biology · 2026Article
- Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential.Life science alliance · 2026Article
- Synergistic interactions and optimal sequencing of chemotherapy and immunotherapy in cancer treatment.Cancer chemotherapy and pharmacology · 2026Review
- Spatial single-cell analysis reveals tumor microenvironment signatures predictive of oral cavity cancer outcome.Cell reports. Medicine · 2026Article
- Culture Dimensionality Modulates Gallium Maltolate Response in Glioblastoma: Comparative Analyses in 2D and 3D Models.Molecular pharmaceutics · 2026Article
- The fluoropyrimidine polymer CF10 synergizes with 5-ethynyl-2'-deoxyuridine by promoting telomere attrition and mitotic catastrophe.NAR molecular medicine · 2026Article
- Article
- MTHFR allele and one-carbon metabolic profile predict severity of COVID-19.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- TP53-dependent antitumor effects of DHODH Inhibition in nasopharyngeal carcinoma.Discover oncology · 2025Article
152 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Over the past 60 years, chemotherapeutic agents that target thymidylate biosynthesis and the enzyme thymidylate synthase (TS) have remained among the most-successful drugs used in the treatment of cancer. Fluoropyrimidines, such as 5-fluorouracil and capecitabine, and antifolates, such as methotrexate and pemetrexed, induce a state of thymidylate deficiency and imbalances in the nucleotide pool that impair DNA replication and repair. TS-targeted agents are used to treat numerous solid and haematological malignancies, either alone or as foundational therapeutics in combination treatment regimens. We overview the pivotal discoveries that led to the rational development of thymidylate biosynthesis as a chemotherapeutic target, and highlight the crucial contribution of these advances to driving and accelerating drug development in the earliest era of cancer chemotherapy. The function of TS as well as the mechanisms and consequences of inhibition of this enzyme by structurally diverse classes of drugs with distinct mechanisms of action are also discussed. In addition, breakthroughs relating to TS-targeted therapies that transformed the clinical landscape in some of the most-difficult-to-treat cancers, such as pancreatic, colorectal and non-small-cell lung cancer, are highlighted. Finally, new therapeutic agents and novel mechanism-based strategies that promise to further exploit the vulnerabilities and target resistance mechanisms within the thymidylate biosynthesis pathway are reviewed.
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Registered trials
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.