Trial reportAnnals of oncology : official journal of the European Society for Medical Oncology2017
Impact of genetic variations in the MAPK signaling pathway on outcome in metastatic colorectal cancer patients treated with first-line FOLFIRI and bevacizumab: data from FIRE-3 and TRIBE trials.
Trial report 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 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- MAP3K1 rs889312 polymorphism and cancer prognosis: A systematic review and meta-analysis.Cancer reports (Hoboken, N.J.) · 2023Pooled it
- VEGF-A, VEGFR1 and VEGFR2 single nucleotide polymorphisms and outcomes from the AGITG MAX trial of capecitabine, bevacizumab and mitomycin C in metastatic colorectal cancer.Scientific reports · 2022Trial
- Decoding colorectal cancer targeted therapy: a bibliometric journey of the last decade (2015-2024).Discover oncology · 2025Article
- Exploring MAP3K genes in gastric cancer: biomarkers, tumor microenvironment dynamics, and chemotherapy resistance.Hereditas · 2025Article
- Rbms3 Upregulation in Mesenchymal Stem Cells Impairs Fracture Healing in Type 2 Diabetes Mellitus.Journal of inflammation research · 2025Article
- 10-hydroxy-2-decenoic acid prevents osteoarthritis by targeting aspartyl β hydroxylase and inhibiting chondrocyte senescence in male mice preclinically.Nature communications · 2024Article
- Review
- A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.Journal of cellular and molecular medicine · 2023Article
- Review
- Article
- MiR-323a regulates ErbB3/EGFR and blocks gefitinib resistance acquisition in colorectal cancer.Cell death & disease · 2022Article
- A Genetic Variant inFrontiers in oncology · 2022Article
- Suppression of AGTR1 Induces Cellular Senescence in Hepatocellular Carcinoma Through Inactivating ERK Signaling.Frontiers in bioengineering and biotechnology · 2022Article
- A novel tumour suppressor protein encoded by circMAPK14 inhibits progression and metastasis of colorectal cancer by competitively binding to MKK6.Clinical and translational medicine · 2021Article
- Article
- Analysis of KRAS Mutation Status Prediction Model for Colorectal Cancer Based on Medical Imaging.Computational and mathematical methods in medicine · 2021Article
- MAGI2-AS3 rs7783388 polymorphism contributes to colorectal cancer risk through altering the binding affinity of the transcription factor GR to the MAGI2-AS3 promoter.Journal of clinical laboratory analysis · 2020Article
- Phosphorylation of the mRNA cap-binding protein eIF4E and cancer.Cellular signalling · 2020Review
- Combination of variations in inflammation- and endoplasmic reticulum-associated genes as putative biomarker for bevacizumab response in KRAS wild-type colorectal cancer.Scientific reports · 2020Article
- The p38 MAPK Signaling Activation in Colorectal Cancer upon Therapeutic Treatments.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe MAPK-interacting kinase 1 (MKNK1) is localized downstream of the RAS/RAF/ERK and the MAP3K1/MKK/p38 signaling pathway. Through phosphorylation MKNK1 regulates the function of eukaryotic translation initiation factor 4E, a key player in translational control, whose expression is often upregulated in metastatic colorectal cancer patients (mCRC). Preclinical data suggest that MKNK1 increases angiogenesis by upregulating angiogenic factors. We therefore hypothesize that variations in the MKNK1 gene predict outcome in mCRC patients treated with first-line FOLFIRI and bevacizumab (bev). PATIENTS AND
methodsA total of 567 patients with KRAS wild-type mCRC in the randomized phase III FIRE-3 and TRIBE trials treated with first-line FOLFIRI/bev (discovery and validation cohorts) or FOLFIRI and cetuximab (cet) (control cohort) were included in this study. Five single-nucleotide polymorphisms in the MAPK signaling pathway were analyzed.
resultsAA genotype carriers of the MKNK1 rs8602 single-nucleotide polymorphism treated with FOLFIRI/bev in the discovery cohort (FIRE-3) had a shorter progression-free survival (PFS) than those harboring any C (7.9 versus 10.3 months, Hazard ratio (HR) 1.73, P = 0.038). This association could be confirmed in the validation cohort (TRIBE) in multivariable analysis (PFS 9.0 versus 11.0 months, HR 3.04, P = 0.029). Furthermore, AA carriers in the validation cohort had a decreased overall response rate (25% versus 66%, P = 0.049). Conversely, AA genotype carriers in the control group receiving FOLFIRI/cet did not show a shorter PFS. By combining both FOLFIRI/bev cohorts the worse outcome among AA carriers became more significant (PFS 9.0 versus 10.5 months) in univariable (HR 1.74, P = 0.015) and multivariable analysis (HR 1.76, P = 0.022). Accordingly, AA carriers did also exhibit an inferior overall response rate compared with those harboring any C (36% versus 65%, P = 0.005).
conclusionMKNK1 polymorphism rs8602 might serve as a predictive marker in KRAS wild-type mCRC patients treated with FOLFIRI/bev in the first-line setting. Additionally, MKNK1 might be a promising target for drug development.
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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.