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    GENE:

    TYMS (Thymidylate Synthetase)

    i
    Other names: TYMS, Thymidylate Synthetase, Thymidylate Synthase, TSase, HST422, TMS
    2d
    Mebendazole impairs the expression and function of enzymes in nucleotide metabolism pathways, leading to Selective Cytotoxicity, Cell Cycle Arrest, and Damage to Cell Morphology in Gastric Cancer. (PubMed, Chem Biol Interact)
    Our findings suggest that MBZ modulates nucleotide synthesis pathways, contributing to its selective antiproliferative effects in GC cells. This study highlights potential new pharmacological targets for drug repurposing and further investigation into the broader therapeutic applications of MBZ.
    Journal
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    TYMS (Thymidylate Synthetase) • PRPS1 (Phosphoribosyl Pyrophosphate Synthetase 1) • HPRT1 (Hypoxanthine Phosphoribosyltransferase 1)
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    5-fluorouracil • mebendazole
    2d
    ECOG 6293: Phase II Study of Raltitrexed in Advanced Colorectal Cancer. (PubMed, Oncologist)
    In this phase II trial, raltitrexed did not show significant response rates in patients with advanced CRC. Due to limited ORR of raltitrexed, value of TS expression as a biomarker was inconclusive. No new safety signals for raltitrexed were demonstrated.
    P2 data • Journal
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    TYMS (Thymidylate Synthetase)
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    5-fluorouracil • leucovorin calcium • Tomudex (raltitrexed)
    10d
    Panobinostat Potentiates the Antitumor Efficacy of 5-Fluorouracil in Gastric Cancer by Suppressing Thymidylate Synthase Expression. (PubMed, Int J Mol Sci)
    Furthermore, panobinostat downregulated a network of oncogenes and cell cycle regulators, including c-Myc and key cyclins. These findings indicate that panobinostat can enhance 5-FU cytotoxicity by targeting TS expression and reprogramming oncogenic transcriptional networks, supporting its potential as a complementary strategy for overcoming fluoropyrimidine resistance in GC therapy.
    Journal
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    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • TYMS (Thymidylate Synthetase)
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    5-fluorouracil • Farydak (panobinostat)
    13d
    Development and validation of a prognosis model for low-grade gliomas based on metabolic gene risk scoring and immune microenvironment interaction. (PubMed, Discov Oncol)
    This study constructed and validated a metabolism-driven prognostic model. The model enables prognostic stratification of LGG patients and links high-risk scores to metabolic dysregulation and an immunosuppressive microenvironment characterized by M2 macrophage enrichment, based on multi-omics data. Mechanistic exploration indicates this association is particularly pronounced in myeloid cells, predominantly within metabolism-related M2 macrophage subpopulations. Furthermore, computational analysis suggests differences in drug sensitivity between risk groups and identifies potential therapeutic compounds, providing clues for future exploration of therapeutic strategies targeting metabolic-immune interactions.
    Journal • Tumor mutational burden
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    TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TYMS (Thymidylate Synthetase) • CYP17A1 (Cytochrome P450 Family 17 Subfamily A Member 1) • GLRX (Glutaredoxin) • ACACB (Acetyl-CoA Carboxylase Beta) • GPX7 (Glutathione Peroxidase 7) • ALOX15B (Arachidonate 15-Lipoxygenase Type B)
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    IDH1 mutation
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    AZD6482
    16d
    Effects of thymidylate synthase inhibitors differ in genomic uracilation and mutagenic potential. (PubMed, Life Sci Alliance)
    Previously, we established that treating HCT116 colon cancer cell lines with either raltitrexed (RTX) or 5-fluoro-2'-deoxyuridine (5FdUR), two potent inhibitors of thymidylate synthase, results in characteristic genomic uracil patterns...The mutational spectra and the clustered nature of these transitions suggested the involvement of APOBEC3 DNA cytidine deaminases, several of which were induced under these conditions. Notably, this mutagenic response coincides with decreased cytotoxicity compared with the low-dose 5FdUR or any efficient doses of RTX, providing insights that may be relevant for personalized cancer therapy.
    Journal
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    TYMS (Thymidylate Synthetase)
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    Tomudex (raltitrexed)
    19d
    Integrated multi-dataset screening to predict prognosis and identify immunotherapy gene targets in hepatocellular carcinoma patients. (PubMed, Sci Rep)
    Candidate genes were closely associated with features of the immune microenvironment, showing significant correlations with levels of immune cell infiltration and expression of immune checkpoint molecules such as PD-1 and CTLA-4. This study identified core HCC genes with prognostic and immunotherapeutic significance, providing novel targets and a theoretical basis for optimizing risk stratification and personalized treatment.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    PD-1 (Programmed cell death 1) • TYMS (Thymidylate Synthetase)
    20d
    LNP-Mediated CF10 Delivery Selectively Enhances Potency to Colorectal Cancer Cells and Preserves the TS/Top1 Dual Targeting Mechanism. (PubMed, ACS Appl Bio Mater)
    The nanoscale DNA-based fluoropyrimidine polymer CF10 shows strong efficacy advantages relative to conventional fluoropyrimidine drugs such as 5-fluorouracil (5-FU)...CF10:LNPs also efficiently induced Top1 cleavage complex formation, consistent with perturbation of cellular dNTP pools similar to free CF10. These findings indicate that CF10:LNPs display enhanced anticancer activity relative to free CF10 and preserve CF10's unique TS/Top1 dual targeting mechanism.
    Journal
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    TYMS (Thymidylate Synthetase)
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    5-fluorouracil
    27d
    Alterations in the transcriptional profile of genes in tumors as a prerequisite for personalization of treatment in breast cancer patients (PubMed, Arkh Patol)
    Comparative mRNA expression analysis confirms that a short preoperative course of aromatase inhibitors induces a more potent and uniform molecular response, characterized by profound suppression of proliferation and complete inhibition of estrogen-dependent signaling. Tamoxifen therapy is also effective but results in less pronounced suppression of key targets and, crucially, may be accompanied by early activation of the MYC oncogene, a potential marker for resistance development.
    Journal • PD(L)-1 Biomarker • IO biomarker
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    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • PGR (Progesterone receptor) • PTEN (Phosphatase and tensin homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • CCNE1 (Cyclin E1) • FGFR4 (Fibroblast growth factor receptor 4) • BIRC5 (Baculoviral IAP repeat containing 5) • TYMS (Thymidylate Synthetase) • AURKA (Aurora kinase A) • FOXA1 (Forkhead Box A1) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • PTTG1 (PTTG1 Regulator Of Sister Chromatid Separation, Securin) • BAG1 (BAG Cochaperone 1) • EMSY (EMSY Transcriptional Repressor BRCA2 Interacting) • GATA3 (GATA binding protein 3) • KRT5 (Keratin 5) • MMP11 (Matrix Metallopeptidase 11) • MYBL2 (MYB Proto-Oncogene Like 2) • SFRP1 (Secreted frizzled related protein 1) • TMEM45B (Transmembrane Protein 45B) • ANLN (Anillin Actin Binding Protein) • CCNB1 (Cyclin B1) • SCGB2A2 (Secretoglobin Family 2A Member 2) • ZNF703 (Zinc Finger Protein 703)
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    HER-2 negative • HER-2 expression
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    tamoxifen • letrozole • anastrozole
    1m
    Machine learning-assisted detection of canine mammary tumors using serum autoantibody signatures. (PubMed, Vet Q)
    This proof-of-concept study demonstrates that a machine learning-assisted multiplex autoantibody assay offers a feasible noninvasive approach for CMT detection. Further validation in larger, independent cohorts is warranted to support clinical translation in veterinary oncology.
    Journal
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    TYMS (Thymidylate Synthetase) • AGR2 (Anterior gradient 2) • IGFBP5 (Insulin Like Growth Factor Binding Protein 5)
    1m
    Targeting thymidylate synthase enhances CD8 + T-cell infiltration and inhibits tumor growth in cervical cancer. (PubMed, Med Oncol)
    Molecular docking identified Deoxyuridine Monophosphate as a high-affinity inhibitor of TYMS. Our findings demonstrate that targeting thymidylate synthase enhances CD8 + T-cell infiltration and inhibits tumor growth in cervical cancer, establishing TYMS as a promising therapeutic target.
    Journal • IO biomarker
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    CD8 (cluster of differentiation 8) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • TYMS (Thymidylate Synthetase) • CD4 (CD4 Molecule) • MRC1 (Mannose Receptor C-Type 1) • MYO6 (Myosin VI) • SPINT1 (Serine Peptidase Inhibitor, Kunitz Type 1)
    1m
    Bridging mechanism and design: modern medicinal chemistry approaches to thymidylate synthase inhibitors. (PubMed, RSC Adv)
    Moreover, innovative strategies such as noncatalytic enzyme destabilizers, hybrid multitarget inhibitors, and biomarker-guided prodrug systems are reshaping the future of TS-directed therapeutics. This review highlights the structural evolution of TS inhibitors from classical to next-generation agents, bridging mechanistic understanding with the design of safer and more effective anticancer drugs.
    Review • Journal
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    TYMS (Thymidylate Synthetase)
    1m
    Design, Synthesis, and Anticancer Assessment of Benzylated Pyrrole-Based Pyrido[2,3-d]Pyrimidines as Thymidylate Synthase Inhibitors. (PubMed, Chem Biol Drug Des)
    Compounds 1c and 2i exhibited potent TS inhibition with IC50 values of 11.50 ± 1.08 nM and 17.12 ± 0.91 nM, respectively, comparable to the standard drug raltitrexed (IC50 = 12.51 ± 0.91 nM)...Additionally, compounds 1c and 2i exhibited good stability in 300 ns molecular dynamics simulations along with acceptable drug-like properties and oral bioavailability. These findings suggest that compounds 1c and 2i are promising lead candidates for the development of TS inhibitors.
    Journal
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    TYMS (Thymidylate Synthetase)
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    Tomudex (raltitrexed)