ArticleEuropean journal of cancer (Oxford, England : 1990)2017
Potential role of polymorphisms in the transporter genes ENT1 and MATE1/OCT2 in predicting TAS-102 efficacy and toxicity in patients with refractory metastatic colorectal cancer.
Article in European journal of cancer (Oxford, England : 1990), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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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
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Human equilibrative nucleoside transporter 1 and concentrative nucleoside transporter 1 in colorectal cancer: What do we know? A systematic review.Histology and histopathology · 2025Pooled it
- 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
- Preclinical identification and clinical validation of dynamic biomarkers for trifluridine/tipiracil with or without bevacizumab in metastatic colorectal cancer.ESMO gastrointestinal oncology · 2026Article
- Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.International journal of molecular sciences · 2025Review
- Article
- Impact of genetic variants in the solute carrier (Cancer drug resistance (Alhambra, Calif.) · 2024Review
- Prognostic impact of severe neutropenia in colorectal cancer patients treated with TAS-102 and bevacizumab, addressing immortal-time bias.BMC cancer · 2023Article
- Targeting the multidrug and toxin extrusion 1 gene (SLC47A1) sensitizes glioma stem cells to temozolomide.American journal of cancer research · 2023Article
- Nucleoside transporters and immunosuppressive adenosine signaling in the tumor microenvironment: Potential therapeutic opportunities.Pharmacology & therapeutics · 2022Review
- Biomarkers of Trifluridine-Tipiracil Efficacy.Journal of clinical medicine · 2021Review
- Review
- Genetic Heterogeneity of SLC22 Family of Transporters in Drug Disposition.Journal of personalized medicine · 2018Review
- Efficacy and safety of TAS-102 in refractory metastatic colorectal cancer: a meta-analysis.Cancer management and research · 2018Article
- Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication.Scientific reports · 2017Article
- Safety and Efficacy of Trifluridine-Tipiracil Hydrochloride Oral Combination (TAS-102) in Patients with Unresectable Colorectal Cancer.In vivo (Athens, Greece)Article
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundTrifluridine (FTD) is an active cytotoxic component of the metastatic colorectal cancer (mCRC) drug TAS-102, and thymidine phosphorylase inhibitor (TPI) inhibits the rapid degradation of FTD. We tested whether single nucleotide polymorphisms (SNPs) in genes involved in FTD metabolism and TPI excretion could predict outcome in patients with mCRC treated with TAS-102. PATIENTS AND
methodsWe investigated three different cohorts: a training cohort (n = 52) and a testing cohort (n = 129) both receiving TAS-102 and a control cohort (n = 52) receiving regorafenib. SNPs of TK1, ENT1, CNT1, MATE1, MATE2 and OCT2 were analysed by polymerase chain reaction-based direct DNA sequencing.
resultsIn the training cohort, patients with any ENT1 rs760370 G allele had a significantly longer progression-free survival (PFS; 3.5 versus 2.1 months, respectively, hazard ratio [HR] 0.44, P = 0.004) and overall survival (OS; 8.7 versus 5.3 months, respectively, HR 0.27, P = 0.003) than the A/A genotype. These findings were validated in the testing cohort (P = 0.021 and 0.009 for PFS and OS, respectively). In addition, the combination of ENT1 rs760370, MATE1 rs2289669 and OCT2 rs316019 SNPs significantly stratified patients with the risk of PFS and OS in both cohorts (P < 0.001 for PFS and OS in the training cohort; P = 0.053 and 0.025 for PFS and OS, respectively, in the testing cohort). No significant differences were observed in the control group.
conclusionsThe combination of ENT1, MATE1 and OCT2 SNPs may serve as a predictive and prognostic marker in mCRC patients treated with TAS-102.
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