ReviewMolecular aspects of medicine2017
Targeting nuclear thymidylate biosynthesis.
Review in Molecular aspects of medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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.
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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
35 citing papers in PubMed, 84 citations in OpenAlex.
- Bridging mechanism and design: modern medicinal chemistry approaches to thymidylate synthase inhibitors.RSC advances · 2026Review
- Article
- Article
- DHFR2 RNA directly regulates dihydrofolate reductase and its expression level impacts folate one carbon metabolism.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- Folate metabolism in myelofibrosis: a missing key?Annals of hematology · 2025Review
- Targeting amino acid in tumor therapy.Frontiers in oncology · 2025Review
- Nicotinamide Mononucleotide (NMN) Works in Type 2 Diabetes through Unexpected Effects in Adipose Tissue, Not by Mitochondrial Biogenesis.International journal of molecular sciences · 2024Article
- Study on the Mechanism of UMI-77 in the Treatment of Sepsis-Induced Acute Lung Injury Based on Transcriptomics and Metabolomics.Journal of inflammation research · 2024Article
- Enzyme kinetics of deoxyuridine triphosphatase from Western corn rootworm.BMC research notes · 2023Article
- Review
- Nuclear PTEN Regulates Thymidylate Biosynthesis in Human Prostate Cancer Cell Lines.Metabolites · 2023Article
- Pemetrexed induces ROS generation and cellular senescence by attenuating TS-mediated thymidylate metabolism to reverse gefitinib resistance in NSCLC.Journal of cellular and molecular medicine · 2023Article
- New Natural Eugenol Derivatives as Antiproliferative Agents: Synthesis, Biological Evaluation, and Computational Studies.ACS omega · 2023Article
- Endothelial cell metabolism in sepsis.World journal of emergency medicine · 2023Review
- Review of 5-FU resistance mechanisms in colorectal cancer: clinical significance of attenuated on-target effects.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Alterations of microbiota and metabolites in the feces of calves with diarrhea associated with rotavirus and coronavirus infections.Frontiers in microbiology · 2023Article
- Metabolomic analysis and pharmacological validation of the cerebral protective effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury.Molecular medicine reports · 2023Article
- Thymidylate synthase accelerates Men1-mediated pancreatic tumor progression and reduces survival.JCI insight · 2022Article
- Early Life Stage Folic Acid Deficiency Delays the Neurobehavioral Development and Cognitive Function of Rat Offspring by Hindering De Novo Telomere Synthesis.International journal of molecular sciences · 2022Article
- Cytosolic localization and in vitro assembly of human de novo thymidylate synthesis complex.The FEBS journal · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Thymidylate (dTMP) biosynthesis plays an essential and exclusive function in DNA synthesis and proper cell division, and therefore has been an attractive therapeutic target. Folate analogs, known as antifolates, and nucleotide analogs that inhibit the enzymatic action of the de novo thymidylate biosynthesis pathway and are commonly used in cancer treatment. In this review, we examine the mechanisms by which the antifolate 5-fluorouracil, as well as other dTMP synthesis inhibitors, function in cancer treatment in light of emerging evidence that dTMP synthesis occurs in the nucleus. Nuclear localization of the de novo dTMP synthesis pathway requires modification of the pathway enzymes by the small ubiquitin-like modifier (SUMO) protein. SUMOylation is required for nuclear localization of the de novo dTMP biosynthesis pathway, and disruption in the SUMO pathway inhibits cell proliferation in several cancer models. We summarize evidence that the nuclear localization of the dTMP biosynthesis pathway is a critical factor in the efficacy of antifolate-based therapies that target dTMP synthesis.
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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.