ArticleOncogene2020
Hexosamine pathway inhibition overcomes pancreatic cancer resistance to gemcitabine through unfolded protein response and EGFR-Akt pathway modulation.
Article in Oncogene, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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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
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 43 citations in OpenAlex.
- PGM3 insufficiency: a glycosylation disorder causing a notable T cell defect.Frontiers in immunology · 2024Pooled it
- Meta-analysis of the effect of PGM on survival prognosis of tumor patients.Frontiers in oncology · 2022Pooled it
- HMHLVI: Hybrid Multi-view Hypergraph Learning with Variational Inference for snoRNA-Drug Association Prediction.Interdisciplinary sciences, computational life sciences · 2026Article
- Mitochondria-targeted metformin analogs activate the ER stress-unfolded protein response pathway to drive apoptosis in pancreatic cancer.Cell death & disease · 2026Article
- PSMD11 stabilizes PGM3 by antagonizing Parkin to promote bladder cancer progression through energy metabolism reprogramming.Cell death & disease · 2026Article
- Review
- Targeting the SYVN1-EGFR axis: a breakthrough strategy for TKI-resistant NSCLC.Cell death & disease · 2025Article
- The HBP Pathway Inhibitor FR054 Enhances Temozolomide Sensitivity in Glioblastoma Cells by Promoting Ferroptosis and Inhibiting O-GlcNAcylation.CNS neuroscience & therapeutics · 2025Article
- Targeting PGM3 abolishes SREBP-1 activation-hexosamine synthesis feedback regulation to effectively suppress brain tumor growth.Science advances · 2025Article
- Endoplasmic Reticulum Stress in Cancer Progression: A Comprehensive Review of Its Role and Mechanisms.International journal of medical sciences · 2025Review
- Oncometabolites in pancreatic cancer: Strategies and its implications.World journal of experimental medicine · 2024Review
- GFPT2 expression is induced by gemcitabine administration and enhances invasion by activating the hexosamine biosynthetic pathway in pancreatic cancer.Clinical & experimental metastasis · 2024Article
- Endoplasmic reticulum stress-a key guardian in cancer.Cell death discovery · 2024Review
- Glucose metabolism in B cell malignancies: a focus on glycolysis branching pathways.Molecular oncology · 2024Review
- Targeting cancer metabolic pathways for improving chemotherapy and immunotherapy.Cancer letters · 2023Review
- Review
- Serum thrombospondin-1 serves as a novel biomarker and agonist of gemcitabine-based chemotherapy in intrahepatic cholangiocarcinoma.British journal of cancer · 2023Article
- PGM3 inhibition shows cooperative effects with erastin inducing pancreatic cancer cell deathFrontiers in oncology · 2023Article
- The crosstalk among the physical tumor microenvironment and the effects of glucose deprivation on tumors in the past decade.Frontiers in cell and developmental biology · 2023Review
- PGM3 regulates beta-catenin activity to promote colorectal cancer cell progression.Experimental biology and medicine (Maywood, N.J.) · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Different evidence has indicated metabolic rewiring as a necessity for pancreatic cancer (PC) growth, invasion, and chemotherapy resistance. A relevant role has been assigned to glucose metabolism. In particular, an enhanced flux through the Hexosamine Biosynthetic Pathway (HBP) has been tightly linked to PC development. Here, we show that enhancement of the HBP, through the upregulation of the enzyme Phosphoacetylglucosamine Mutase 3 (PGM3), is associated with the onset of gemcitabine (GEM) resistance in PC. Indeed, mRNA profiles of GEM sensitive and resistant patient-derived tumor xenografts (PDXs) indicate that PGM3 expression is specifically increased in GEM-resistant PDXs. Of note, PGM3 results also overexpressed in human PC tissues as compared to paired adjacent normal tissues and its higher expression in PC patients is associated with worse median overall survival (OS). Strikingly, genetic or pharmacological PGM3 inhibition reduces PC cell growth, migration, invasion, in vivo tumor growth and enhances GEM sensitivity. Thus, combined treatment between a specific inhibitor of PGM3, named FR054, and GEM results in a potent reduction of xenograft tumor growth without any obvious side effects in normal tissues. Mechanistically, PGM3 inhibition, reducing protein glycosylation, causes a sustained Unfolded Protein Response (UPR), a significant attenuation of the pro-tumorigenic Epidermal Growth Factor Receptor (EGFR)-Akt axis, and finally cell death. In conclusion this study identifies the HBP as a metabolic pathway involved in GEM resistance and provides a strong rationale for a PC therapy addressing the combined treatment with the PGM3 inhibitor and GEM.
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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.