ArticleBritish journal of cancer2018
MTOR inhibitor-based combination therapies for pancreatic cancer.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study.Targeted oncology · 2018Trial
- Dual Targeting of FGFR4 and PI3K-mTOR Suppresses Tumor-Associated Phenotypes in Pancreatic Ductal Adenocarcinoma.International journal of molecular sciences · 2026Article
- Inference of upstream-mutation and metabolomic-signature causality identifies prognostic biomarkers and therapeutic targets in pancreatic cancer.Nature communications · 2026Article
- Review
- Drivers of Pancreatic Cancer: Beyond the Big 4.Cancers · 2025Review
- Inhibition of the PI3K/AKT/mTOR pathway in pancreatic cancer: is it a worthwhile endeavor?Therapeutic advances in medical oncology · 2024Review
- Copy Number Variations in Pancreatic Cancer: From Biological Significance to Clinical Utility.International journal of molecular sciences · 2023Review
- SHP2 clinical phenotype, cancer, or RASopathies, can be predicted by mutant conformational propensities.Cellular and molecular life sciences : CMLS · 2023Article
- Exploiting Vitamin D Receptor and Its Ligands to Target Squamous Cell Carcinomas of the Head and Neck.International journal of molecular sciences · 2023Article
- Lysosomal lipid switch sensitises to nutrient deprivation and mTOR targeting in pancreatic cancer.Gut · 2023Article
- Glycogen Synthase Kinase 3β: A True Foe in Pancreatic Cancer.International journal of molecular sciences · 2022Review
- Indirect targeting of MYC sensitizes pancreatic cancer cells to mechanistic target of rapamycin (mTOR) inhibition.Cancer communications (London, England) · 2022Article
- The Impact of Epithelial-Mesenchymal Transition and Metformin on Pancreatic Cancer Chemoresistance: A Pathway towards Individualized Therapy.Medicina (Kaunas, Lithuania) · 2022Review
- A low amino acid environment promotes cell macropinocytosis through the YY1-FGD6 axis in Ras-mutant pancreatic ductal adenocarcinoma.Oncogene · 2022Article
- Network controllability solutions for computational drug repurposing using genetic algorithms.Scientific reports · 2022Article
- Determination of a DNA repair-related gene signature with potential implications for prognosis and therapeutic response in pancreatic adenocarcinoma.Frontiers in oncology · 2022Article
- Rationale for MYC imaging and targeting in pancreatic cancer.EJNMMI research · 2021Review
- Article
- Apatinib inhibits pancreatic cancer growth, migration and invasion through the PI3K/AKT and ERK1/2/MAPK pathways.Translational cancer research · 2021Article
- Article
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Authors and funding
17 authors at 10 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAlthough the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification.
methodsWe used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pharmacological intervention studies were used to recapitulate genetic data in human models, including primary human 3D PDAC cultures.
resultsGenetic deletion of the Mtor gene in the pancreas results in exocrine and endocrine insufficiency. In established murine PDAC cells, MTOR is linked to metabolic pathways and maintains the glucose uptake and growth. Importantly, blocking MTOR genetically as well as pharmacologically results in adaptive rewiring of oncogenic signalling with activation of canonical extracellular signal-regulated kinase and phosphoinositide 3-kinase-AKT pathways. We provide evidence that interfering with such adaptive signalling in murine and human PDAC models is important in a subgroup.
conclusionsOur data suggest developing dual MTORC1/TORC2 inhibitor-based therapies for subtype-specific intervention.
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