ArticleInternational journal of oncology2015
Crucial roles of thymidine kinase 1 and deoxyUTPase in incorporating the antineoplastic nucleosides trifluridine and 2'-deoxy-5-fluorouridine into DNA.
Article in International journal of oncology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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.
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.
Who cites it
34 citing papers in PubMed, 57 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
- The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer.European journal of cancer (Oxford, England : 1990) · 2018Trial
- Nucleotide Metabolism in Health and Disease.MedComm · 2026Review
- Trifluridine/tipiracil enhances radiation-induced abscopal effects and augments PD-1 blockade in gastric cancer.Scientific reports · 2026Article
- Incorporation and Repair of Epigenetic Intermediates as Potential Chemotherapy Agents.Molecules (Basel, Switzerland) · 2025Article
- Total neoadjuvant therapy integrating long-course radiotherapy with trifluridine/tipiracil for locally advanced rectal cancer: a single-arm, multicenter phase 2 trial.EClinicalMedicine · 2025Article
- Impact of renal function on non-hematologic toxicities in mCRC patients treated with TAS-102: a post-hoc analysis of the JASCC-CINV2001 study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Observational
- Renal impairment as a risk factor for chemotherapy induced neutropenia in the treatment of trifluridine/thymidine phosphorylase inhibitor plus bevacizumab.Scientific reports · 2025Article
- The emerging emetogenicity of trifluridine/tipiracil (TAS‑102) from patient self-reporting: a multicenter, prospective, observational study.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Observational
- A Retrospective Study of Trifluridine/Tipiracil with Fruquintinib in Patients with Chemorefractory Metastatic Colorectal Cancer.Journal of clinical medicine · 2023Article
- Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias.BMC cancer · 2023Article
- Article
- A phase 1b multicenter study of TAS-102 in combination with irinotecan in patients with advanced recurrent or unresectable gastric and gastroesophageal adenocarcinoma after at least one line of treatment with a fluoropyrimidine and platinum-containing regimen.Medical oncology (Northwood, London, England) · 2022Article
- Severe pancytopenia caused by trifluridine/tipiracil in patients with metastatic colorectal cancer and an impaired renal function: A case report.Clinical case reports · 2022Article
- Biomarkers of Trifluridine-Tipiracil Efficacy.Journal of clinical medicine · 2021Review
- Issues and limitations of available biomarkers for fluoropyrimidine-based chemotherapy toxicity, a narrative review of the literature.ESMO open · 2021Review
- Detection of trifluridine in tumors of patients with metastatic colorectal cancer treated with trifluridine/tipiracil.Cancer chemotherapy and pharmacology · 2020Article
- Bevacizumab in Combination with TAS-102 Improves Clinical Outcomes in Patients with Refractory Metastatic Colorectal Cancer: A Retrospective Study.The oncologist · 2020Article
- β-Elemene Reverses the Resistance of p53-Deficient Colorectal Cancer Cells to 5-Fluorouracil by Inducing Pro-death Autophagy and Cyclin D3-Dependent Cycle Arrest.Frontiers in bioengineering and biotechnology · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Trifluridine (FTD) and 2'-deoxy-5-fluorouridine (FdUrd), a derivative of 5-fluorouracil (5-FU), are antitumor agents that inhibit thymidylate synthase activity and their nucleotides are incorporated into DNA. However, it is evident that several differences occur in the underlying antitumor mechanisms associated with these nucleoside analogues. Recently, TAS-102 (composed of FTD and tipiracil hydrochloride, TPI) was shown to prolong the survival of patients with colorectal cancer who received a median of 2 prior therapies, including 5-FU. TAS-102 was recently approved for clinical use in Japan. These data suggest that the antitumor activities of TAS-102 and 5-FU proceed via different mechanisms. Thus, we analyzed their properties in terms of thymidine salvage pathway utilization, involving membrane transporters, a nucleoside kinase, a nucleotide-dephosphorylating enzyme, and DNA polymerase α. FTD incorporated into DNA with higher efficiency than FdUrd did. Both FTD and FdUrd were transported into cells by ENT1 and ENT2 and were phosphorylated by thymidine kinase 1, which showed a higher catalytic activity for FTD than for FdUrd. deoxyUTPase (DUT) did not recognize dTTP and FTD-triphosphate (F3dTTP), whereas deoxyuridine-triphosphate (dUTP) and FdUrd-triphosphate (FdUTP) were efficiently degraded by DUT. DNA polymerase α incorporated both F3dTTP and FdUTP into DNA at sites aligned with adenine on the opposite strand. FTD-treated cells showed differing nuclear morphologies compared to FdUrd-treated cells. These findings indicate that FTD and FdUrd are incorporated into DNA with different efficiencies due to differences in the substrate specificities of TK1 and DUT, causing abundant FTD incorporation into DNA.
Indexed as
Identifiers
What OpenQuestion holds
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.