ArticleScientific reports2020
Real-time metabolic profiling of oesophageal tumours reveals an altered metabolic phenotype to different oxygen tensions and to treatment with Pyrazinib.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers, 1 of them a synthesis that pooled it.
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Who cites it
6 citing papers in PubMed, 1 synthesis or guideline pooled it, 10 citations in OpenAlex.
- Potential Predictive Immune and Metabolic Biomarkers of Tumor Microenvironment Regarding Pathological and Clinical Response in Esophageal Cancer After Neoadjuvant Chemoradiotherapy: A Systematic Review.Annals of surgical oncology · 2024Pooled it
- Methods and Guidelines for Metabolism Studies: Applications to Cancer Research.International journal of molecular sciences · 2025Review
- Targeting Radiation Resistance in Oesophageal Adenocarcinoma with Pyrazinib-Functionalised Gold Nanoparticles.Cancers · 2024Article
- Energy Metabolism Is Altered in Radioresistant Rectal Cancer.International journal of molecular sciences · 2023Article
- Article
- Metformin is a metabolic modulator and radiosensitiser in rectal cancer.Frontiers in oncology · 2023Article
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Oesophageal cancer is the 6th most common cause of cancer related death worldwide. The current standard of care for oesophageal adenocarcinoma (OAC) focuses on neoadjuvant therapy with chemoradiation or chemotherapy, however the 5-year survival rates remain at < 20%. To improve treatment outcomes it is critical to further investigate OAC tumour biology, metabolic phenotype and their metabolic adaptation to different oxygen tensions. In this study, by using human ex-vivo explants we demonstrated using real-time metabolic profiling that OAC tumour biopsies have a significantly higher oxygen consumption rate (OCR), a measure of oxidative phosphorylation compared to extracellular acidification rate (ECAR), a measure of glycolysis (p = 0.0004). Previously, we identified a small molecule compound, pyrazinib which enhanced radiosensitivity in OAC. Pyrazinib significantly inhibited OCR in OAC treatment-naïve biopsies (p = 0.0139). Furthermore, OAC biopsies can significantly adapt their metabolic rate in real-time to their environment. Under hypoxic conditions pyrazinib produced a significant reduction in both OCR (p = 0.0313) and ECAR in OAC treatment-naïve biopsies. The inflammatory secretome profile from OAC treatment-naïve biopsies is heterogeneous. OCR was positively correlated with three secreted factors in the tumour conditioned media: vascular endothelial factor A (VEGF-A), IL-1RA and thymic stromal lymphopoietin (TSLP). Pyrazinib significantly inhibited IL-1β secretion (p = 0.0377) and increased IL-3 (p = 0.0020) and IL-17B (p = 0.0181). Importantly, pyrazinib did not directly alter the expression of dendritic cell maturation markers or reduce T-cell viability or activation markers. We present a new method for profiling the metabolic rate of tumour biopsies in real-time and demonstrate the novel anti-metabolic and anti-inflammatory action of pyrazinib ex-vivo in OAC tumours, supporting previous findings in-vitro whereby pyrazinib significantly enhanced radiosensitivity in OAC.
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