Metabolic Regulation of Angiogenesis in Pancreatic Ductal Adenocarcinoma.

Authors

Xin Ye, Zihan Wang, Ping Wang

Published in

Journal of visualized experiments : JoVE. Issue 236. Oct 01, 2026. Epub Oct 01, 2026.

Abstract

​Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal, with a 5‑year survival of only 13%. Its aggressive biology and late diagnosis often lead to metastatic spread at presentations. This review examines how metabolic reprogramming regulates angiogenesis in PDAC and explores the therapeutic implications of this coupling. We systematically analyzed published studies on glucose, amino acid, and lipid metabolic alterations and their interconnection with neovascularization through hypoxia-inducible factor-1α (HIF-1α), oncogenic signaling, and metabolite-mediated pathways. Based on a synthesis of the current literature, metabolic-angiogenic coupling appears to operate through at least three interconnected mechanisms: the HIF‑1α/pyruvate kinase M2 (PKM2)-driven glycolytic-vascular endothelial growth factor (VEGF) axis; lactate acting as a signaling molecule that promotes M2‑polarized tumor‑associated macrophages and stabilizes HIF‑1α; and lipid metabolites--including eicosanoids and fatty acid‑binding protein 4 (FABP4)-that modulate endothelial function and survival. In addition, glutamine-derived intermediates support endothelial sprouting and extracellular matrix remodeling, while tryptophan and serine pathways influence the immune-angiogenic balance. Importantly, compensatory pathways (e.g., HIF-1α-independent angiogenesis via glycogen accumulation and protease-activated receptor‑2 activation) limit the efficacy of single‑agent interventions, highlighting the need for combination strategies. Understanding these metabolic-angiogenic networks provides a rationale for biomarker‑guided therapies that simultaneously target tumor metabolism and vascularization. Integrating metabolic and angiogenic biomarkers (e.g., VEGF, lactate dehydrogenase A) with imaging-based metabolic profiling may improve patient stratification and treatment monitoring in PDAC.

PMID:
42825501
Bibliographic data and abstract were imported from PubMed on 02 Oct 2026.

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