ArticleClinical cancer research : an official journal of the American Association for Cancer Research2019
Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 66 citations in OpenAlex.
- Patient-derived organoids reveal ductal dysfunction and CFTR-modulator responses in chronic pancreatitis.Cell stem cell · 2026Article
- Inhibition of Focal Adhesion Restricts Chemoresistance in Pancreatic Cancer by Targeting SLC7A11 Mediated Ferroptosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Organoids: From Bench to Bedside Applications.MedComm · 2026Review
- KRAS Inhibition in Pancreatic Ductal Adenocarcinoma.Journal of clinical medicine · 2026Review
- Patient-derived organoids guide personalized therapy for KRAS-mutant pancreatic cancer: synergistic MEK/mTOR inhibition and predictive chemotherapy responses.Frontiers in immunology · 2026Article
- Chronic pancreatitis patient-derived organoids reveal new paths to precision therapeutics.bioRxiv : the preprint server for biology · 2025Article
- Endocrine cancer organoids in basic and translational medical research.Science China. Life sciences · 2025Review
- Experimental models of pancreas cancer: what has been the impact for precision medicine?The Journal of clinical investigation · 2025Review
- Establishing Pancreatic Cancer Organoids from EUS-Guided Fine-Needle Biopsy Specimens.Cancers · 2025Review
- Advancing pancreatic cancer research and therapeutics: the transformative role of organoid technology.Experimental & molecular medicine · 2025Review
- Machine learning and gene network integration reveal prognostic subnetworks and biomarkers in pancreatic cancer.Computational and structural biotechnology journal · 2025Article
- Expression of fibroblast growth factor receptor 1 correlates inversely with the efficacy of single-agent fibroblast growth factor receptor-specific inhibitors in pancreatic cancer.British journal of pharmacology · 2024Article
- Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation.Clinical epigenetics · 2024Article
- Glutamine mimicry suppresses tumor progression through asparagine metabolism in pancreatic ductal adenocarcinoma.Nature cancer · 2024Article
- Signature-driven repurposing of Midostaurin for combination with MEK1/2 and KRASG12C inhibitors in lung cancer.Nature communications · 2023Article
- Dual Inhibition of KRASG12D and Pan-ERBB Is Synergistic in Pancreatic Ductal Adenocarcinoma.Cancer research · 2023Article
- Streamlined DNA-encoded small molecule library screening and validation for the discovery of novel chemotypes targeting BET proteins.Molecular therapy. Nucleic acids · 2023Article
- USP9X mediates an acute adaptive response to MAPK suppression in pancreatic cancer but creates multiple actionable therapeutic vulnerabilities.Cell reports. Medicine · 2023Article
- Scaffolding Protein Connector Enhancer of Kinase Suppressor of Ras 1 (CNKSR1) Regulates MAPK Inhibition Responsiveness in Pancreas Cancer via Crosstalk with AKT Signaling.Molecular cancer research : MCR · 2023Article
- Review
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Authors and funding
19 authors at 1 institution in 1 country.
Funding
Abstract
purposeEXPERIMENTAL
designWe evaluated the expression and activation of receptor tyrosine kinases in response to combined MEK and AKT inhibition in KPC mice and pancreatic ductal organoids. In addition, we sought to determine the therapeutic efficacy of targeting resistance pathways induced by MEK and AKT inhibition in order to identify malignant-specific vulnerabilities.
resultsCombined MEK and AKT inhibition modestly extended the survival of KPC mice and increased Egfr and ErbB2 phosphorylation levels. Tumor organoids, but not their normal counterparts, exhibited elevated phosphorylation of ERBB2 and ERBB3 after MEK and AKT blockade. A pan-ERBB inhibitor synergized with MEK and AKT blockade in human PDA organoids, whereas this was not observed for the EGFR inhibitor erlotinib. Combined MEK and ERBB inhibitor treatment of human organoid orthotopic xenografts was sufficient to cause tumor regression in short-term intervention studies.
conclusionsAnalyses of normal and tumor pancreatic organoids revealed the importance of ERBB activation during MEK and AKT blockade primarily in the malignant cultures. The lack of ERBB hyperactivation in normal organoids suggests a larger therapeutic index. In our models, pan-ERBB inhibition was synergistic with dual inhibition of MEK and AKT, and the combination of a pan-ERBB inhibitor with MEK antagonists showed the highest activity both
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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.