Grobbelaar, C.W. (Craig)Steenkamp, VanessaMabeta, Peaceful Lucy2025-11-252025-11-252025-03Grobbelaar, C.; Steenkamp, V. & Mabeta, P. Vascular Endothelial Growth Factor Receptors in the Vascularization of Pancreatic Tumors: Implications for Prognosis and Therapy. Current Issues in Molecular Biology 2025, 47, 179. https://doi.org/10.3390/cimb47030179.1467-3037 (print)1467-3045 (online)10.3390/cimb4703017910.3390/cimb47030179http://hdl.handle.net/2263/105483In pancreatic cancer (PC), vascular endothelial growth factor (VEGF) and its primary receptor, vascular endothelial growth factor receptor (VEGFR)-2, are central drivers of angiogenesis and metastasis, with their overexpression strongly associated with poor prognosis. In some PC patients, VEGF levels correlate with disease stage, tumor burden, and survival outcomes. However, therapies targeting VEGF and VEGFR-2, including tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, have demonstrated limited efficacy, partly due to the emergence of resistance mechanisms. Resistance appears to stem from the activation of alternative vascularization pathways. This review explores the multifaceted roles of VEGFRs in pancreatic cancer, including VEGFR-1 and VEGFR-3. Potential strategies to improve VEGFR-targeting therapies, such as combination treatments, the development of more selective inhibitors, and the use of biomarkers, are discussed as promising approaches to enhance treatment efficacy and outcomes.en© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.VEGFR-1VEGFR-2VEBFR-3Pancreatic cancer (PCa)AngiogenesisLymphangiogenesisMetastasisHypoxiaTumor microenvironmentVascular homeostasisVascular endothelial growth factor (VEGF)Article