Abstract
Angiogenesis is a crucial event in tumor development and progression, occurring by different mechanisms and it is driven by pro- and anti-angiogenic molecules. Pancreatic cancer vascularization is characterized by a high microvascular density, impaired microvessel integrity and poor perfused vessels with heterogeneous distribution. In this review article, after a brief introduction on pancreatic cancer classification and on angiogenesis mechanisms involved in its progression, the pre-clinical and clinical trials conducted in pancreatic cancer treatment using anti-angiogenic inhibitors will be described. Finally, we will discuss the anti-angiogenic therapy paradox between the advantage to abolish vessel supply to block tumor growth and the disadvantage due to reduction of drug delivery at the same time. The purpose is to identify new anti-angiogenic molecules that may enhance treatment regimen.
Highlights
Pancreatic cancer is the seventh leading cause of cancer death in the world in 2018, with an incidence of 2.5% and a mortality of 4.5% [1]
It has been demonstrated that the serum levels of angiogenic cytokines, such as VEGF and interleukin 8 (IL-8), are associated with tumor progression in pancreatic neuroendocrine tumor patients, and they might use as biomarkers for prognosis and therapy [52]
For these reasons it is expected that anti-angiogenic therapy will be effective in both pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors with the aim to block blood vessels growth to stop cancer cells growth [19]
Summary
Pancreatic cancer is the seventh leading cause of cancer death in the world in 2018, with an incidence of 2.5% and a mortality of 4.5% [1]. It has a higher incidence in high/very high developed countries compare to low/medium developed countries [1]. The major part (>95%) are cancers of exocrine gland and these are mostly (>85%) pancreatic ductal adenocarcinomas, that via lymph vascular system metastasize to organs, such as liver [7,8]. Cancers of the endocrine gland, called pancreatic neuroendocrine tumors are less common (1–2% of all pancreatic cancer in Europe) and are most often benign [13]. Given the high heterogeneity of pancreatic cancer, an accurate characterization of different types by origin, degree and metastasis presence/absence and their localization, are crucial in order to adopt the most appropriate therapy
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