ArticleOncotarget2015
Rational combination of MEK inhibitor and the STAT3 pathway modulator for the therapy in K-Ras mutated pancreatic and colon cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- A Phase Ia/b study of MEK1/2 inhibitor binimetinib with MET inhibitor crizotinib in patients with RAS mutant advanced colorectal cancer (MErCuRIC).BMC cancer · 2025Article
- Navigating the Molecular Signaling: Deciphering Cancer Stem Cell Self-Renewal Pathways.International journal of molecular and cellular medicine · 2025Review
- Targeting Stem Cells and Dysplastic Features With Dual MEK/ERK and STAT3 Suppression in Gastric Carcinogenesis.Gastroenterology · 2024Article
- Article
- Polydopamine Copolymers for Stable Drug Nanoprecipitation.International journal of molecular sciences · 2022Article
- STAT signaling as a target for intervention: from cancer inflammation and angiogenesis to non-coding RNAs modulation.Molecular biology reports · 2022Review
- Role of Nrf2, STAT3, and Src as Molecular Targets for Cancer Chemoprevention.Pharmaceutics · 2022Review
- Discoveries in Pancreatic Physiology and Disease Biology Using Single-Cell RNA Sequencing.Frontiers in cell and developmental biology · 2021Review
- Modeling Adaptive Resistance of KRAS Mutant Colorectal Cancer to MAPK Pathway Inhibitors with a Three-Dimensional Tumor Model.ACS pharmacology & translational science · 2020Article
- Review
- Antitumor activity of a novel oral signal transducer and activator of transcription 3 inhibitor YHO-1701.Cancer science · 2020Article
- Feedback activation of EGFR is the main cause for STAT3 inhibition-irresponsiveness in pancreatic cancer cells.Oncogene · 2020Article
- Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors.Oncology letters · 2020Review
- Entrectinib resistance mechanisms in ROS1-rearranged non-small cell lung cancer.Investigational new drugs · 2020Article
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- Article
- Article
- Rhein sensitizes human pancreatic cancer cells to EGFR inhibitors by inhibiting STAT3 pathway.Journal of experimental & clinical cancer research : CR · 2019Article
- Rhein sensitizes human colorectal cancer cells to EGFR inhibitors by inhibiting STAT3 pathway.OncoTargets and therapy · 2019Article
- STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells.Oncogene · 2019Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
Abstract
K-Ras mutations are frequently detected in pancreatic and colon cancers, which are associated with the resistance to MEK inhibitors targeting the Ras pathway. Identifying the underlying mechanisms for the acquired resistance is essential for the future clinical development of MEK inhibitors. Here, we identified that Signal Transducer and Activator of Transcription 3 (STAT3) was significantly activated following the MEK inhibition using AZD6244, PD98059 and Trametinib in K-Ras mutant pancreatic and colon cancer cells. The STAT3 activation may be important for the MEK inhibitor resistance in these K-Ras mutant cancer cells. We have shown that dual inhibition of STAT3 and MEK using the STAT3 inhibitor LY5 and MEK inhibitor Trametinib exerts significant anti-tumor cell efficacy in K-Ras mutant pancreatic and colon cancer cells in vitro. In addition, Trametinib showed increased suppression on tumor growth in vivo in STAT3 knockdown pancreatic cancer cells compared with tumor growth of control cells without STAT3 knockdown. Taken together, our results suggest the induced STAT3 activation as a possible mechanism for the resistance to MEK inhibitor and demonstrate the potentials of a combination therapy using MEK and STAT3 inhibitors in pancreatic and colon cancers harboring K-Ras mutant proteins.
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Registered trials
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.