ArticleScientific reports2019
Cytotoxicity of trifluridine correlates with the thymidine kinase 1 expression level.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 21 citations in OpenAlex.
- TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial.British journal of cancer · 2024Trial
- Monitoring FTD in the peripheral blood mononuclear cells of elderly patients with metastatic colorectal cancer administered FTD plus bevacizumab as first-line treatment.Cancer science · 2021Trial
- Stable Gold@Polydopamine@ssDNA Bioconjugates for Highly Efficient Detection of Tumor-Related mRNA in Living Cells.Molecules (Basel, Switzerland) · 2025Article
- Leveraging autophagy and pyrimidine metabolism to target pancreatic cancer.bioRxiv : the preprint server for biology · 2025Article
- The anti-tumor effect of trifluridine via induction of aberrant mitosis is unaffected by mutations modulating p53 activity.Cell death discovery · 2024Article
- Synthesis of Fluorinated Nucleosides/Nucleotides and Their Antiviral Properties.Molecules (Basel, Switzerland) · 2024Review
- AZD6738 promotes the tumor suppressive effects of trifluridine in colorectal cancer cells.Oncology reports · 2023Article
- Biomarkers of Trifluridine-Tipiracil Efficacy.Journal of clinical medicine · 2021Review
- Mechanism of acquired 5FU resistance and strategy for overcoming 5FU resistance focusing on 5FU metabolism in colon cancer cell lines.Oncology reports · 2021Article
- Morphological Profiling Identifies a Common Mode of Action for Small Molecules with Different Targets.Chembiochem : a European journal of chemical biology · 2020Article
- Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.Cancer chemotherapy and pharmacology · 2020Article
- TAS-102 has a tumoricidal activity in multiple myeloma.American journal of cancer research · 2020Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trifluridine (FTD), a tri-fluorinated thymidine analogue, is a key component of the oral antitumor drug FTD/TPI (also known as TAS-102), which is used to treat refractory metastatic colorectal cancer. Thymidine kinase 1 (TK1) is thought to be important for the incorporation of FTD into DNA, resulting in DNA dysfunction and cytotoxicity. However, it remains unknown whether TK1 is essential for FTD incorporation into DNA and whether this event is affected by the expression level of TK1 because TK1-specific-deficient human cancer cell lines have not been established. Here, we generated TK1-knock-out human colorectal cancer cells using the CRISPR/Cas9 genome editing system and validated the specificity of TK1 knock-out by measuring expression of AFMID, which is encoded on the same locus as TK1. Using TK1-knock-out cells, we confirmed that TK1 is essential for cellular sensitivity to FTD. Furthermore, we demonstrated a correlation between the TK1 expression level and cytotoxicity of FTD using cells with inducible TK1 expression, which were generated from TK1-knock-out cells. Based on our finding that the TK1 expression level correlates with sensitivity to FTD, we suggest that FTD/TPI might efficiently treat cancers with high TK1 expression.
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