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.
