ArticleJournal of molecular medicine (Berlin, Germany)2011
Autophagy suppression promotes apoptotic cell death in response to inhibition of the PI3K-mTOR pathway in pancreatic adenocarcinoma.
Article in Journal of molecular medicine (Berlin, Germany), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
57 citing papers in PubMed, 101 citations in OpenAlex.
- SMAD4 loss is associated with response to neoadjuvant chemotherapy plus hydroxychloroquine in patients with pancreatic adenocarcinoma.Clinical and translational science · 2021Trial
- Safety and Biologic Response of Pre-operative Autophagy Inhibition in Combination with Gemcitabine in Patients with Pancreatic Adenocarcinoma.Annals of surgical oncology · 2015Trial
- Modulation of the PI3K/Akt signaling pathway by resveratrol in cancer: molecular mechanisms and therapeutic opportunity.Discover oncology · 2025Review
- Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023Review
- Turning up the heat on non-immunoreactive tumors: autophagy influences the immune microenvironment in pancreatic cancer.BMC medical genomics · 2022Article
- Regulation and function of autophagy in pancreatic cancer.Autophagy · 2021Review
- Encouraging long-term survival following autophagy inhibition using neoadjuvant hydroxychloroquine and gemcitabine for high-risk patients with resectable pancreatic carcinoma.Cancer medicine · 2021Review
- Review
- Oridonin induces autophagy-mediated cell death in pancreatic cancer by activating the c-Jun N-terminal kinase pathway and inhibiting phosphoinositide 3-kinase signaling.Annals of translational medicine · 2021Article
- RETRACTED: Tioconazole and Chloroquine Act Synergistically to Combat Doxorubicin-Induced Toxicity via Inactivation of PI3K/AKT/mTOR Signaling Mediated ROS-Dependent Apoptosis and Autophagic Flux Inhibition in MCF-7 Breast Cancer Cells.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Anti-tumor activity of resveratrol against gastric cancer: a review of recent advances with an emphasis on molecular pathways.Cancer cell international · 2021Review
- Facing Cell Autophagy in Gastric Cancer - What Do We Know so Far?International journal of general medicine · 2021Review
- Polyamine Blocking Therapy Decreases Survival of Tumor-Infiltrating Immunosuppressive Myeloid Cells and Enhances the Antitumor Efficacy of PD-1 Blockade.Molecular cancer therapeutics · 2020Article
- The synergistic anti-proliferative effect of the combination of diosmin and BEZ-235 (dactolisib) on the HCT-116 colorectal cancer cell line occurs through inhibition of the PI3K/Akt/mTOR/NF-κB axis.Molecular biology reports · 2020Article
- Combination Therapy with a PI3K/mTOR Dual Inhibitor and Chloroquine Enhances Synergistic Apoptotic Cell Death in Epstein-Barr Virus-Infected Gastric Cancer Cells.Molecules and cells · 2019Article
- Therapeutic Potency of PI3K Pharmacological Inhibitors of Gastrointestinal Cancer.Middle East journal of digestive diseases · 2019Review
- Article
- Combined inhibition of the PI3K/mTOR/MEK pathway induces Bim/Mcl-1-regulated apoptosis in pancreatic cancer cells.Cancer biology & therapy · 2019Article
- A Novel Polyamine-Targeted Therapy for BRAF Mutant Melanoma Tumors.Medical sciences (Basel, Switzerland) · 2018Article
- Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Targeting of pathways downstream of RAS represents a promising therapeutic strategy for pancreatic cancer, the fourth leading cause of cancer-related death in the USA, since activation of the Raf-MEK-ERK and PI3K-AKT pathways is found frequently in this disease and is associated with poor prognosis. Taking advantage of a panel of human PDAC cell lines and specific inhibitors of PI3K and/or mTOR, we systematically address the question whether dual-targeted inhibition of the PI3K and mTOR pathways offers advantages over single-targeted inhibition of PI3K in PDAC. We observe greater overall susceptibility of cell lines to dual inhibition compared to targeting PI3K alone. However, we find that dual inhibition of PI3K and mTOR induces autophagy to a greater extent than inhibition of each target alone. In agreement with this, we show that combined administration of PI3K/mTOR and autophagy inhibitors results in increased anti-tumor activity in vitro and in vivo in models of pancreatic adenocarcinoma. XL765, a PI3K/mTOR inhibitor used in our in vivo studies, is currently undergoing clinical evaluation in a variety of cancer types, while the autophagy inhibitor chloroquine is a widely used anti-malaria compound. Thus, our studies provide rationale for clinical development of combinations of these compounds for the treatment of pancreatic adenocarcinoma.
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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.