ArticleAnticancer research2017
MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines.
Article in Anticancer research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 13 citations in OpenAlex.
- Molecular and clinical registry of Chilean patients diagnosed with BRAF-mutated colorectal cancer.Journal of gastrointestinal oncology · 2025Article
- PA-MSHA exerts potent activity against cetuximab-resistant colorectal cancer through the miR-7-5p/Akt3/Wnt-β-catenin pathway.Translational cancer research · 2024Article
- Overexpression of sortilin is associated with 5-FU resistance and poor prognosis in colorectal cancer.Journal of cellular and molecular medicine · 2021Article
- Clarithromycin inhibits autophagy in colorectal cancer by regulating the hERG1 potassium channel interaction with PI3K.Cell death & disease · 2020Article
- Pharmacological effects of the simultaneous and sequential combinations of trifluridine/tipiracil (TAS-102) and 5-fluorouracil in fluoropyrimidine-sensitive colon cancer cells.Investigational new drugs · 2020Article
- Enhanced antitumor effect of binimetinib in combination with capecitabine for biliary tract cancer patients with mutations in the RAS/RAF/MEK/ERK pathway: phase Ib study.British journal of cancer · 2019Article
- Article
- MEK inhibitor enhanced the antitumor effect of oxaliplatin and 5‑fluorouracil in MEK1 Q56P‑mutant colorectal cancer cells.Molecular medicine reports · 2019Article
- Redox-responsive self-assembly PEG nanoparticle enhanced triptolide for efficient antitumor treatment.Scientific reports · 2018Article
- The Dual PI3K/mToR Inhibitor Omipalisib/GSK2126458 Inhibits Clonogenic Growth in Oncogenically-transformed Cells from Neurocutaneous Melanocytosis.Cancer genomics & proteomicsArticle
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundPreclinical evidence demonstrates that mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway inhibition increases sensitivity to 5-fluorouracil (5-FU) in colorectal cancer (CRC) cell lines and xenografts. Here, we aimed to investigate how CRC cell sensitivity to this combination is correlated to Kirsten rat sarcoma (KRAS) and proto-oncogene B-rapidly accelerated fibrosarcoma (BRAF) mutation, that are common in CRC and often lead to resistance to chemotherapy. MATERIALS AND
methodsWild-type and mutant KRAS/BRAF human CRC cell lines were treated with escalating doses of 5-FU or trifluridine with MEK162 (MEK1/2 inhibitor) for 72 h. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and synergism expressed by the combination index was calculated using CalcuSyn.
resultsEvidence of synergistic antitumor activity was observed for the majority of human CRC cell lines treated with MEK162 plus 5-FU (4/6) or trifluridine (7/9). Synergism was greater in KRAS- or BRAF-mutant cell lines compared to wild-type KRAS/BRAF CRC cell lines.
conclusionThe combination of MEK inhibition and trifluridine is worthwhile advancing in clinical development, particularly for treatment-refractory KRAS- or BRAF-mutated metastatic CRC.
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