ArticleBritish journal of cancer2019
Targeting β-catenin overcomes MEK inhibition resistance in colon cancer with KRAS and PIK3CA mutations.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 45 citations in OpenAlex.
- Unravelling Resistance: Integrating Metabolism, Epigenetics, Immunology, and Proteostasis in Strategies against Kirsten Rat Sarcoma Viral Oncogene Homolog-mutant Colorectal Cancer.International journal of biological sciences · 2026Review
- Comprehensive analysis of PIK3CA mutations in advanced colorectal cancer using circulating tumor DNA profiling.NPJ precision oncology · 2025Article
- ENTR1 affects the progression of colon cancer by regulating energy metabolism under the influence of glycolysis.BMC cancer · 2025Article
- The effect of novel nitrogen-based chalcone analogs on colorectal cancer cells: Insight into the molecular pathways.Heliyon · 2024Article
- Cellular and Molecular Mechanisms of the Tumor Stroma in Colorectal Cancer: Insights into Disease Progression and Therapeutic Targets.Biomedicines · 2023Review
- Tumor microenvironment involvement in colorectal cancer progressionWorld journal of gastroenterology · 2022Review
- PIK3CA mutations-mediated downregulation of circLHFPL2 inhibits colorectal cancer progression via upregulating PTEN.Molecular cancer · 2022Article
- Conquering oncogenic KRAS and its bypass mechanisms.Theranostics · 2022Review
- WNT as a Driver and Dependency in Cancer.Cancer discovery · 2021Review
- MEK inhibitors - novel targeted therapies of neurofibromatosis associated benign and malignant lesions.Biomarker research · 2021Review
- Are Wnt/β-Catenin and PI3K/AKT/mTORC1 Distinct Pathways in Colorectal Cancer?Cellular and molecular gastroenterology and hepatology · 2020Review
- An integrative pharmacogenomics analysis identifies therapeutic targets in KRAS-mutant lung cancer.EBioMedicine · 2019Article
- EZH2 inhibition suppresses bladder cancer cell growth and metastasis via the JAK2/STAT3 signaling pathway.Oncology letters · 2019Article
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Authors and funding
23 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMitogen-activated protein kinases (MEK 1/2) are central components of the RAS signalling pathway and are attractive targets for cancer therapy. These agents continue to be investigated in KRAS mutant colon cancer but are met with significant resistance. Clinical investigations have demonstrated that these strategies are not well tolerated by patients.
methodsWe investigated a biomarker of response for MEK inhibition in KRAS mutant colon cancers by LC-MS/MS analysis. We tested the MEK inhibitor in PIK3CA wild(wt) and mutant(mt) colon cancer cells. In addition, we tested the combinational effects of MEK and TNKS inhibitor in vitro and in vivo.
resultsWe identified β-catenin, a key mediator of the WNT pathway, in response to MEK inhibitor. MEK inhibition led to a decrease in β-catenin in PIK3CA wt colon cancer cells but not in mt. Tumour regression was promoted by combination of MEK inhibition and NVP-TNS656, which targets the WNT pathway. Furthermore, inhibition of MEK promoted tumour regression in colon cancer patient-derived xenograft models expressing PIK3CA wt.
conclusionsWe propose that inhibition of the WNT pathway, particularly β-catenin, may bypass resistance to MEK inhibition in human PIK3CA mt colon cancer. Therefore, we suggest that β-catenin is a potential predictive marker of MEK inhibitor resistance.
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