ArticleAnnals of oncology : official journal of the European Society for Medical Oncology2017
Genetic variants of DNA repair-related genes predict efficacy of TAS-102 in patients with refractory metastatic colorectal cancer.
Article in Annals of oncology : official journal of the European Society for Medical Oncology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 2 of them syntheses that pooled it.
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.
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
18 citing papers in PubMed, 2 syntheses or guidelines pooled it, 28 citations in OpenAlex.
- ATM is associated with the prognosis of colorectal cancer: a systematic review.Frontiers in oncology · 2025Pooled it
- Genomic and epigenomic biomarkers in colorectal cancer: From diagnosis to therapy.Advances in cancer research · 2021Pooled it
- TAS-102, Irinotecan, and bevacizumab in pre-treated metastatic colorectal cancer (TABAsCO), a phase II clinical trial.British journal of cancer · 2024Trial
- A randomized, phase 2 study of deoxyuridine triphosphatase inhibitor, TAS-114, in combination with S-1 versus S-1 alone in patients with advanced non-small-cell lung cancer.Investigational new drugs · 2020Trial
- Preclinical identification and clinical validation of dynamic biomarkers for trifluridine/tipiracil with or without bevacizumab in metastatic colorectal cancer.ESMO gastrointestinal oncology · 2026Article
- Trifluridine/tipiracil with or without bevacizumab in microsatellite instability-high/mismatch repair-deficient metastatic colorectal cancer: A retrospective observational study.Therapeutic advances in medical oncology · 2026Article
- Article
- Roles of peptidyl-prolyl isomerase Pin1 in disease pathogenesis.Theranostics · 2021Review
- Exploiting DNA repair defects in colorectal cancer.Molecular oncology · 2019Review
- Predictive Biomarkers in Metastatic Colorectal Cancer: A Systematic Review.JCO precision oncology · 2019Review
- Feasibility and effectiveness of trifluridine/tipiracil in metastatic colorectal cancer: real-life data from The Netherlands.International journal of clinical oncology · 2018Article
- Observational
- Monitoring trifluridine incorporation in the peripheral blood mononuclear cells of colorectal cancer patients under trifluridine/tipiracil medication.Scientific reports · 2017Article
- Profile of trifluridine/tipiracil hydrochloride in the treatment of metastatic colorectal cancer: efficacy, safety, and place in therapy.OncoTargets and therapy · 2017Review
- Synergistic anticancer activity of a novel oral chemotherapeutic agent containing trifluridine and tipiracil in combination with anti-PD-1 blockade in microsatellite stable-type murine colorectal cancer cells.American journal of cancer research · 2017Article
- Emerging combination therapies for metastatic colorectal cancer - impact of trifluridine/tipiracil.Cancer management and research · 2017Review
- TAS-102 and the quest for predictive biomarkers.ESMO open · 2017Article
- Article
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 3 countries.
Funding
Abstract
Background: Tri-phosphorylated trifluridine (FTD) incorporation into DNA is TAS-102's main anti-tumor action. We tested whether genetic polymorphisms in homologous recombination (HR) and cell cycle checkpoint pathway for DNA repair is associated with outcomes in refractory metastatic colorectal cancer (mCRC) patients treated with TAS-102. Patients and methods: We analyzed genomic DNA extracted from 233 samples of three cohorts: an evaluation cohort of 52 patients receiving TAS-102, a validation cohort of 129 patients receiving TAS-102 and a control cohort of 52 patients receiving regorafenib. Single nucleotide polymorphisms of genes involved in HR (ATM, BRCA1, BRCA2, XRCC3, FANCD2, H2AX, RAD51) and cell cycle checkpoint (ATR, CHEK1, CHEK2, CDKN1A, TP53, CHE1, PIN1, PCNA) were analyzed by PCR-based direct sequencing. Results: In univariate analysis for the evaluation cohort, patients with any G allele in ATM rs609429 had longer overall survival (OS) than those with the C/C variant (8.7 vs. 4.4 months, HR 0.37, 95% CI: 0.14-0.99, P = 0.022). Patients carrying any A allele in XRCC3 rs861539 had significantly longer progression-free survival (PFS) (3.8 vs. 2.3 months, HR 0.44, 95% CI: 0.21-0.92, P = 0.024) and OS (15.6 vs. 6.3 months, HR 0.25, 95% CI: 0.08-0.79, P = 0.012) than those with the G/G variant. In multivariable analysis, ATM rs609429 remained significant for OS (P = 0.020). In the validation cohort, patients having ATM rs609429 with any G allele showed longer OS and PFS; the G/A variant in XRCC3 rs861539 showed longer OS, though without statistical significance. Conclusion: Genetic variants in the HR pathway may predict clinical outcome in mCRC patients receiving TAS-102.
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Registered trials
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