ArticleMolecular cancer therapeutics2009
KRAS/BRAF mutation status and ERK1/2 activation as biomarkers for MEK1/2 inhibitor therapy in colorectal cancer.
Article in Molecular cancer therapeutics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 91 papers.
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Who cites it
91 citing papers in PubMed, 154 citations in OpenAlex.
- A Phase II Trial of AZD6244 (Selumetinib, ARRY-142886), an Oral MEK1/2 Inhibitor, in Relapsed/Refractory Multiple Myeloma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Bcl-2 stabilization by paxillin confers 5-fluorouracil resistance in colorectal cancer.Cell death and differentiation · 2015Trial
- Phase II study of the oral MEK inhibitor selumetinib in advanced acute myelogenous leukemia: a University of Chicago phase II consortium trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Trial
- Phase II study of the mitogen-activated protein kinase 1/2 inhibitor selumetinib in patients with advanced hepatocellular carcinoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011Trial
- Protease-Activated Receptor-2 as a Proteolytic Rheostat in Colorectal and Pancreatic Cancer: From Mechanism to Biomarker-Guided Therapy.International journal of molecular sciences · 2026Review
- Combining fruquintinib with TAS-102 as a promising strategy: antitumor activity in preclinical colorectal and gastric cancer xenograft models.BMC cancer · 2026Article
- Erk inhibitors intercept Erk-mediated negative feedback while imposing cell-cycle arrest and activating p38.iScience · 2026Article
- Targeting MEK1/2 inhibits mitochondrial respiration and redox homeostasis in resistant rectal cancer.Journal of bioenergetics and biomembranes · 2026Article
- Systems-level consequences of low RAF abundance for EGFR-ERK signaling.Biophysical journal · 2026Article
- Erk1Oncogene · 2025Article
- Stochastic pharmacodynamics of a heterogeneous tumour-cell population.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- Progress and Challenges in Targeting BRAFV600E-mutant Colorectal Cancer: Molecular Pathogenesis, Treatment Strategies, and Future Directions - My Experience at Johns Hopkins University.Juntendo medical journal · 2025Review
- CBX3 antagonizes IFNγ/STAT1/PD-L1 axis to modulate colon inflammation and CRC chemosensitivity.EMBO molecular medicine · 2024Article
- Molecular-Targeted Therapy for Tumor-Agnostic Mutations in Acute Myeloid Leukemia.Biomedicines · 2022Review
- A New View of Activating Mutations in Cancer.Cancer research · 2022Article
- Kallikrein-Related Peptidase 6 (KLK6) as a Contributor toward an Aggressive Cancer Cell Phenotype: A Potential Role in Colon Cancer Peritoneal Metastasis.Biomolecules · 2022Article
- KRAS mutation-independent downregulation of MAPK/PI3K signaling in colorectal cancer.Molecular oncology · 2022Article
- Expression of SLC22A18 regulates oxaliplatin resistance by modulating the ERK pathway in colorectal cancer.American journal of cancer research · 2022Article
- RAS specific protease induces irreversible growth arrest via p27 in several KRAS mutant colorectal cancer cell lines.Scientific reports · 2021Article
- Early response in phosphorylation of ribosomal protein S6 is associated with sensitivity to trametinib in colorectal cancer cells.Laboratory investigation; a journal of technical methods and pathology · 2021Article
31 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Phase II clinical trials of mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK) inhibitors are ongoing and ERK1/2 activation is frequently used as a biomarker. In light of the mutational activation of BRAF and KRAS in colorectal cancer, inhibitors of the Raf-MEK-ERK mitogen-activated protein kinase are anticipated to be promising. Previous studies in pancreatic cancer have found little correlation between BRAF/KRAS mutation status and ERK1/2 activation, suggesting that identifying biomarkers of MEK inhibitor response may be more challenging than previously thought. The purpose of this study was to evaluate the effectiveness of MEK inhibitor therapy for colorectal cancer and BRAF/KRAS mutation status and ERK1/2 activation as biomarkers for MEK inhibitor therapy. First, we found that MEK inhibitor treatment impaired the anchorage-independent growth of nearly all KRAS/BRAF mutant, but not wild-type, colorectal cancer cells. There was a correlation between BRAF, but not KRAS, mutation status and ERK1/2 activation. Second, neither elevated ERK1/2 activation nor reduction of ERK1/2 activity correlated with MEK inhibition of anchorage-independent growth. Finally, we validated our cell line observations and found that ERK1/2 activation correlated with BRAF, but not KRAS, mutation status in 190 patient colorectal cancer tissues. Surprisingly, we also found that ERK activation was elevated in normal colonic epithelium, suggesting that normal cell toxicity may be a complication for colorectal cancer treatment. Our results suggest that although MEK inhibitors show promise in colorectal cancer, KRAS/BRAF mutation status, but not ERK activation as previously thought, may be useful biomarkers for MEK inhibitor sensitivity.
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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.