Dual inhibition of MEK1/2 and EGFR synergistically induces caspase-3-dependent apoptosis in EGFR inhibitor-resistant lung cancer cells via BIM upregulation

@article{Song2013DualIO,
  title={Dual inhibition of MEK1/2 and EGFR synergistically induces caspase-3-dependent apoptosis in EGFR inhibitor-resistant lung cancer cells via BIM upregulation},
  author={Ji-Young Song and Choung-Soo Kim and Je-Hwan Lee and Se Jin Jang and Sang-Wook Lee and Jung Jin Hwang and Chulsoo Lim and Gilnam Lee and Jeongbeob Seo and Suk Young Cho and Jene Choi},
  journal={Investigational New Drugs},
  year={2013},
  volume={31},
  pages={1458-1465}
}
SummaryEpidermal growth factor receptor (EGFR) gene mutations activate the KRAS-RAF-MEK-ERK pathway in lung cancer cells. EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib induce apoptosis of cancer cells, but prolonged treatment is often associated with acquired resistance. Here, we identified a novel MEK1/2 inhibitor, CZ0775, and compared its cytotoxic effects to those of AZD6244 (selumetinib) in non-small cell lung cancer (NSCLC) cell lines harboring EGFR mutations. The lapatinib… 
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24 Citations

Lung cancer cells survive epidermal growth factor receptor tyrosine kinase inhibitor exposure through upregulation of cholesterol synthesis

It is demonstrated for the first time that ketoconazole treatment inhibits upregulation of mitochondrial cholesterol and thereby overcomes EGFR‐TKI resistance in lung cancer cells, and is shown to shrink the growth of tumors in an in vivo mouse model of EGFR TKI resistance.

Paxillin confers resistance to tyrosine kinase inhibitors in EGFR-mutant lung cancers via modulating BIM and Mcl-1 protein stability

Evidence is provided indicating that paxillin (PXN) overexpression may confer TKI resistance in EGFR-mutant lung cancer cells, and combining TKI with ERK inhibitors may clinically benefit EGFR -mutant non-small cell lung cancer patients whose tumors exhibit high PXN expression.

Treatment with cucurbitacin B alone and in combination with gefitinib induces cell cycle inhibition and apoptosis via EGFR and JAK/STAT pathway in human colorectal cancer cell lines

Investigation of the apoptotic and antiproliferative effects of CuB as a single agent and in combination with Gef on both HT-29 and HCT-116 cell lines showed that, compared to CuB alone, CuB plus Gef treatment caused a significant growth and cell cycle inhibition and induced apoptosis in both cell lines.

Gefitinib induces non-small cell lung cancer H1650 cell apoptosis through downregulating tumor necrosis factor-related apoptosis-inducing ligand expression levels.

Gefitinib treatment markedly inhibited H 1650 cell viability, induced apoptosis and reduced TRAIL expression levels, and induced NSCLC H1650 cell apoptosis by downregulating TRAil expression levels.

Erlotinib and Trametinib in Patients With EGFR-Mutant Lung Adenocarcinoma and Acquired Resistance to a Prior Tyrosine Kinase Inhibitor

Addition of trametinib to erlotinib in the acquired resistance setting in an unselected population is not efficacious, and future studies should focus on targeted therapies in molecularly selected populations.

The apoptotic effect of simvastatin via the upregulation of BIM in nonsmall cell lung cancer cells

The hypothesis that simvastatin has pro-apoptotic effects in epidermal growth factor receptor (EGFR)-mutated lung cancer cell lines via the upregulation of the expression of the BIM protein is investigated and the potential utility of simVastatin as a BIM-targeted treatment for NSCLC is suggested.

MiR-25 reduces PC-9 / BB 4 cell apoptosis sensitivity induced by gefitinib through downregulating BIM

MiR-25 suppressed PC-9/BB4 cell apoptosis induced by gefitinib through targeting BIM, which may play a role in PC- 9/ BB4 cell drug resistance.

miR-16 regulates proliferation and invasion of lung cancer cells via the ERK/MAPK signaling pathway by targeted inhibition of MAPK kinase 1 (MEK1)

Objective The ERK/MAPK signaling pathway regulates cell proliferation and invasion. MAPK kinase 1 (MEK1) is a protein kinase upstream of ERK that can activate the pathway. Expression of microRNA…

Targeting Discoidin Domain Receptor 1 (DDR1) Signaling and Its Crosstalk with β1-Integrin Emerges as a Key Factor for Breast Cancer Chemosensitization upon Collagen Type 1 Binding

Findings provide evidence for the highly dynamic adaptation of breast cancer cells in maintaining matrix binding to circumvent cytotoxicity and highlight DDR1 signaling as a target for sensitization approaches.

EGFR TKI resistance in lung cancer cells using RNA sequencing and analytical bioinformatics tools.

Several key proteins, including D USP1, DUSP6, GAB2, and FOS, that could be targeted using novel combination therapies to overcome EGFR TKI resistance in lung cancer are revealed.

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