ArticleBritish journal of cancer2012
Intrinsic resistance to selumetinib, a selective inhibitor of MEK1/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells.
Article in British journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 47 citations in OpenAlex.
- Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.Molecular oncology · 2025Article
- EGF-Upregulated lncRNA ESSENCE Promotes Colorectal Cancer Growth through Stabilizing CAD and Ferroptosis Defense.Research (Washington, D.C.) · 2025Article
- Lasting response by vertical inhibition with cetuximab and trametinib in KRAS-mutated colorectal cancer patient-derived xenografts.Molecular oncology · 2023Article
- Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.Cancer discovery · 2021Article
- MEK inhibition reprograms CD8Nature immunology · 2021Article
- Complex roles of cAMP-PKA-CREB signaling in cancer.Experimental hematology & oncology · 2020Review
- Design and synthesis of novel phenylaminopyrimidines with antiproliferative activity against colorectal cancer.RSC advances · 2019Article
- Targeting Trop-2 in solid tumors: future prospects.OncoTargets and therapy · 2019Review
- Targeting CREB Pathway Suppresses Small Cell Lung Cancer.Molecular cancer research : MCR · 2018Article
- Phenformin enhances the therapeutic effect of selumetinib in KRAS-mutant non-small cell lung cancer irrespective of LKB1 status.Oncotarget · 2017Article
- Targeting the MEK signaling pathway in non-small cell lung cancer (NSCLC) patients with RAS aberrations.Therapeutic advances in respiratory disease · 2016Review
- Metformin increases antitumor activity of MEK inhibitors through GLI1 downregulation in LKB1 positive human NSCLC cancer cells.Oncotarget · 2016Article
- Redox Homeostasis and Cellular Antioxidant Systems: Crucial Players in Cancer Growth and Therapy.Oxidative medicine and cellular longevity · 2016Review
- The pleiotropic role of exchange protein directly activated by cAMP 1 (EPAC1) in cancer: implications for therapeutic intervention.Acta biochimica et biophysica Sinica · 2016Review
- The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia.Frontiers in physiology · 2016Article
- Antitumor activity of a potent MEK inhibitor, TAK-733, against colorectal cancer cell lines and patient derived xenografts.Oncotarget · 2015Article
- Src inhibitors act through different mechanisms in Non-Small Cell Lung Cancer models depending on EGFR and RAS mutational status.Oncotarget · 2015Article
- KRAS and HRAS mutations confer resistance to MET targeting in preclinical models of MET-expressing tumor cells.Molecular oncology · 2015Article
- BYL719, a selective inhibitor of phosphoinositide 3-Kinase α, enhances the effect of selumetinib (AZD6244, ARRY-142886) in KRAS-mutant non-small cell lung cancer.Investigational new drugs · 2015Article
- MicroRNA-378-5p suppresses cell proliferation and induces apoptosis in colorectal cancer cells by targeting BRAF.Cancer cell international · 2015Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMEK is activated in ∼40% colorectal cancer (CRC) and 20-30% non-small cell lung cancer (NSCLC). Selumetinib is a selective inhibitor of MEK1/2, which is currently in clinical development.
methodsWe evaluated the effects of selumetinib in vitro and in vivo in CRC and NSCLC cell lines to identify cancer cell characteristics correlating with sensitivity to MEK inhibition.
resultsFive NSCLC and six CRC cell lines were treated with selumetinib and classified according to the median inhibitory concentration (IC(50)) values as sensitive (≤1 μM) or resistant (>1 μM). In selumetinib-sensitive cancer cell lines, selumetinib treatment induced G1 cell-cycle arrest and apoptosis and suppression of tumour growth as xenografts in immunodeficient mice. Evaluation of intracellular effector proteins and analysis of gene mutations showed no correlation with selumetinib sensitivity. Microarray gene expression profiles revealed that the activation of cAMP-dependent protein kinase A (PKA) was associated with MEK inhibitor resistance. Combined targeting of both MEK and PKA resulted in cancer cell growth inhibition of MEK inhibitor-resistant cancer cell lines in vitro and in vivo.
conclusionThis study provides molecular insights to explain resistance to an MEK inhibitor in human cancer cell lines.
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