ArticleOncotarget2015
Inhibition of HIF-1α by PX-478 enhances the anti-tumor effect of gemcitabine by inducing immunogenic cell death in pancreatic ductal adenocarcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 138 citations in OpenAlex.
- HIF inhibition: Current strategies and clinical challenges.Redox biology · 2026Review
- Gemcitabine activates the Hippo signaling pathway and suppresses tumor growth by stabilizing large tumor suppressor kinase 2 through the hypoxia-inducible factor 1-alpha/ubiquitin protein ligase E3 component N-recognin 5 axis.Journal of cell communication and signaling · 2026Article
- Hypoxia-inducible factor 1α inhibitor reduces hippocampal neuronal ferroptosis.Neural regeneration research · 2026Article
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- Luteolin Enhances Anticancer Effects of PX-478 during Hypoxic Response in Metastatic Breast Cancer Cells.Anti-cancer agents in medicinal chemistry · 2026Article
- Myeloid metabolism and its role in immunotherapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Article
- HIF1A-mediated pathways promote euploid cell survival in chromosomally mosaic embryos.bioRxiv : the preprint server for biology · 2025Article
- Fibrotic Fortresses and Therapeutic Frontiers: Pancreatic Stellate Cells and the Extracellular Matrix in Pancreatic Cancer.Cancer medicine · 2025Review
- CircRNA-loaded DC vaccine in combination with low-dose gemcitabine induced potent anti-tumor immunity in pancreatic cancer model.Cancer immunology, immunotherapy : CII · 2025Article
- The role of bHLH-PAS transcription factors in endoplasmic reticulum stress.Frontiers in molecular biosciences · 2025Review
- Targeting hypoxia-inducible factor 1 alpha augments synergistic effects of chemo/immunotherapy via modulating tumor microenvironment in a breast cancer mouse model.BioImpacts : BI · 2025Article
- Targeting protein modification: a new direction for immunotherapy of pancreatic cancer.International journal of biological sciences · 2025Review
- Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade.Journal for immunotherapy of cancer · 2024Article
- Metabolic Roles of HIF1, c-Myc, and p53 in Glioma Cells.Metabolites · 2024Review
- Modulation of macrophage metabolism as an emerging immunotherapy strategy for cancer.The Journal of clinical investigation · 2024Review
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Challenges and Opportunities in Targeting the Complex Pancreatic Tumor Microenvironment.JCO oncology advances · 2024Review
- Stimulators of immunogenic cell death for cancer therapy: focusing on natural compounds.Cancer cell international · 2023Review
- Dual hypoxia-responsive supramolecular complex for cancer target therapy.Nature communications · 2023Article
23 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is the worst prognoses among all the malignancies. Now, gemcitabine (Gem) is the first line chemotherapeutic drug for advanced pancreatic cancer. However, Gem is usually ineffective to the PDAC because of high degree of drug resistance. Hypoxia and immune suppressive milieu are the best-described hallmarks of PDAC; therefore, we investigated the impact of hypoxia inducible factor-1 (HIF-1) inhibitor, PX-478, in combination with Gem on the induction of immunogenic cell death (ICD). We verified that combined treatment with Gem/PX-478 significantly enhanced the anti-tumor effect and increased proportion of tumor infiltrating T-lymphocytes in Panc02-bearing immune-competent but not in immune-deficient mice. Vaccination using Panc02 cell line treated with single agent or in combination showed significant anti-tumor effects. Pancreatic cell lines treated with Gem and PX-478 can induce an increase in eIF2α phosphorylation was correlated with down-regulation of HIF-1α and elicited exposure of CRT and release of HMGB1 and ATP. Only co-treated cells induced DC maturation/phagocytosis and IFN-γ secretion by cytotoxic T lymphocytes. Altogether, combined treatment with Gem/PX-478 showed significantly inhibition on tumor growth and anti-tumor immunization. We propose that inhibition HIF-1α elicits Gem-induced immune response and eliminates PDAC cells by inducing ICD.
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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.