Abstract
Pancreatic cancer (PCa) is acknowledged as a significant contributor to global cancer- related mortality and is widely recognized as one of the most challenging malignant diseases to treat. Pancreatic ductal adenocarcinoma (PDAC), which is the most common type of PCa, is highly aggressive and is mostly incurable. The poor prognosis of this neoplasm is exacerbated by the prevalence of angiogenic molecules, which contribute to stromal stiffness and immune escape. PDAC overexpresses various proangiogenic proteins, including vascular endothelial growth factor (VEGF)-A, and the levels of these molecules correlate with poor prognosis and treatment resistance. Moreover, VEGF-targeting anti-angiogenesis treatments are associated with the onset of resistance due to the development of hypoxia, which in turn induces the production of angiogenic molecules. Furthermore, excessive angiogenesis is one of the hallmarks of the second most common form of PCa, namely, pancreatic neuroendocrine tumor (PNET). In this review, the role of angiogenesis regulators in promoting disease progression in PCa, and the impact of these molecules on resistance to gemcitabine and various therapies against PCa are discussed. Finally, the use of anti-angiogenic agents in combination with chemotherapy and other targeted therapeutic molecules is discussed as a novel solution to overcome current treatment limitations in PCa.
Keywords: Pancreatic ductal adenocarcinoma, angiogenesis modulators, immunotherapy, hypoxia, pancreatic neuroendocrine tumor, immune checkpoint inhibitors.
Current Cancer Drug Targets
Title:Angiogenesis and Pancreatic Cancer: Novel Approaches to Overcome Treatment Resistance
Volume: 24 Issue: 11
Author(s): Craig Grobbelaar, Mpho Kgomo and Peace Mabeta*
Affiliation:
- Department of Physiology, University of Pretoria, CNR Lynnwood Road and Roper Street, Hatfield, 0028South Africa
Keywords: Pancreatic ductal adenocarcinoma, angiogenesis modulators, immunotherapy, hypoxia, pancreatic neuroendocrine tumor, immune checkpoint inhibitors.
Abstract: Pancreatic cancer (PCa) is acknowledged as a significant contributor to global cancer- related mortality and is widely recognized as one of the most challenging malignant diseases to treat. Pancreatic ductal adenocarcinoma (PDAC), which is the most common type of PCa, is highly aggressive and is mostly incurable. The poor prognosis of this neoplasm is exacerbated by the prevalence of angiogenic molecules, which contribute to stromal stiffness and immune escape. PDAC overexpresses various proangiogenic proteins, including vascular endothelial growth factor (VEGF)-A, and the levels of these molecules correlate with poor prognosis and treatment resistance. Moreover, VEGF-targeting anti-angiogenesis treatments are associated with the onset of resistance due to the development of hypoxia, which in turn induces the production of angiogenic molecules. Furthermore, excessive angiogenesis is one of the hallmarks of the second most common form of PCa, namely, pancreatic neuroendocrine tumor (PNET). In this review, the role of angiogenesis regulators in promoting disease progression in PCa, and the impact of these molecules on resistance to gemcitabine and various therapies against PCa are discussed. Finally, the use of anti-angiogenic agents in combination with chemotherapy and other targeted therapeutic molecules is discussed as a novel solution to overcome current treatment limitations in PCa.
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Cite this article as:
Grobbelaar Craig, Kgomo Mpho and Mabeta Peace*, Angiogenesis and Pancreatic Cancer: Novel Approaches to Overcome Treatment Resistance, Current Cancer Drug Targets 2024; 24 (11) . https://dx.doi.org/10.2174/0115680096284588240105051402
DOI https://dx.doi.org/10.2174/0115680096284588240105051402 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
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