ArticleBritish journal of cancer2014
KRAS mutational subtype and copy number predict in vitro response of human pancreatic cancer cell lines to MEK inhibition.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 53 citations in OpenAlex.
- Chaperone directed heterobifunctional molecules circumvent KRASCancer letters · 2025Article
- ERK2-mediated phosphorylation of ZEB1 at S322 enhances PD-L1 expression and EMT, leading to pancreatic cancer progression.Cell communication and signaling : CCS · 2025Article
- CDK4/6 inhibition sensitizes MEK inhibition by inhibiting cell cycle and proliferation in pancreatic ductal adenocarcinoma.Scientific reports · 2024Article
- The GATOR2 complex maintains lysosomal-autophagic function by inhibiting the protein degradation of MiT/TFEs.Molecular cell · 2024Article
- KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.The oncologist · 2022Article
- Antigen Peptide Transporter 1 (TAP1) Promotes Resistance to MEK Inhibitors in Pancreatic Cancers.International journal of molecular sciences · 2022Article
- Mutant KRAS drives metabolic reprogramming and autophagic flux in premalignant pancreatic cells.Cancer gene therapy · 2022Article
- Combined Blockade of MEK and CDK4/6 Pathways Induces Senescence to Improve Survival in Pancreatic Ductal Adenocarcinoma.Molecular cancer therapeutics · 2021Article
- Detection of Chemotherapy-resistant Pancreatic Cancer Using a Glycan Biomarker, sTRA.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Observational
- Small molecule inhibitors in pancreatic cancer.RSC medicinal chemistry · 2020Review
- Binimetinib, a novel MEK1/2 inhibitor, exerts anti-leukemic effects under inactive status of PI3Kinase/Akt pathway.International journal of hematology · 2019Article
- Establishment of pancreatic cancer cell lines with endoscopic ultrasound-guided biopsy via conditionally reprogrammed cell culture.Cancer medicine · 2019Article
- Clinical Implications of NRAS Overexpression in Resectable Pancreatic Adenocarcinoma Patients.Pathology oncology research : POR · 2019Article
- Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-1-regulated apoptosis in pancreatic cancer cells.Cancer biology & therapy · 2019Article
- Arsenite malignantly transforms human prostate epithelial cells in vitro by gene amplification of mutated KRAS.PloS one · 2019Article
- Inhibition of the MEK/ERK pathway augments nab-paclitaxel-based chemotherapy effects in preclinical models of pancreatic cancer.Oncotarget · 2018Article
- Discordancy Partitioning for Validating Potentially Inconsistent Pharmacogenomic Studies.Scientific reports · 2017Article
- Phosphorylation of the C-Raf N Region Promotes Raf Dimerization.Molecular and cellular biology · 2017Article
- MEK162 Enhances Antitumor Activity of 5-Fluorouracil and Trifluridine in KRAS-mutated Human Colorectal Cancer Cell Lines.Anticancer research · 2017Article
- Digital PCR Improves Mutation Analysis in Pancreas Fine Needle Aspiration Biopsy Specimens.PloS one · 2017Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo study the molecular mechanism regulating sensitivity to MEK inhibition in pancreatic cancer cell lines.
methodsA growth inhibition assay determined sensitivity to MEK162 in a panel of 29 pancreatic cancer cell lines. For the same panel, KRAS mutational status and copy-number variation (CNV) was determine using PCR, array CGH and FISH. Two sensitive and two resistant cell lines were further interrogated for difference in baseline and MEK162-induced gene expression, as well as signal transduction using microarray and western blotting. Cell cycle and apoptosis analysis was measured by flow cytometry.
resultsWe report a strong correlation between both specific KRAS mutational subtype and CNV, and sensitivity to MEK inhibition. Cell lines with a KRAS (V12) mutation and KRAS gains or loss (n=7) are ∼10 times more resistant than those having neither a KRAS (V12) mutation nor KRAS CNV (n=14). Significant differences in baseline and MEK162-induced gene expression exist between the sensitive and resistant lines, especially in genes involved in RAS, EGF receptor and PI3K pathways. This was further supported by difference in signal transduction. MEK 162 blocked ERK1/2, as well as inhibited PI3K and S6 and increased p27KIP1 levels in the sensitive lines.
conclusionsGiven the potency of MEK162, it may be a promising new therapy for patients with pancreatic cancer and KRAS mutational subtypes, and CNV may serve as important biomarkers for selecting patients that benefit from MEK-targeting based on these preclinical data.
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