Angiogenesis in pancreatic ductal adenocarcinoma: A controversial issue

Abstract

Pancreatic ductal adenocarcinoma (PDAC) occurs in the majority of cases with early loco-regional spread and distant metastases at diagnosis, leading to dismal prognosis with a 5-year overall survival rate moderately over than 5%. This malignancy is largely resistant to chemotherapy and radiation, but the reasons of the refractoriness to the therapies is still unknown. Evidence is accumulating to indicate that the PDAC microenvironment and vascularity strongly contribute to the clinical features of this disease. In particular, PDAC is characterized by excessive dense extracellular matrix deposition associated to vasculature collapse and hypoxia with low drug delivery, explaining at least partly the low efficacy of antiangiogenic drugs in this cancer. Strategies aimed to modulate tumor stroma favoring vasculature perfusion and chemotherapeutics delivery are under investigation.

Transforming growth factor beta‐induced, an extracellular matrix interacting protein, enhances glycolysis and promotes pancreatic cancer cell migration

“…Thus, there is an urgent need to identify, to validate and to clinically test new molecular therapeutic targets. At cellular and molecular levels, PDAC is characterized by hypovascularization, complex landscape of genomic mutations, altered metabolism and exuberant stromal reaction (desmoplasia) . The latter consists in the deposition of extracellular matrix (ECM) components around cancer cells.…”

Pancreatic Enzyme Replacement Therapy in Pancreatic Cancer

“…Liver metastases can result in a liver impairment with reduced chemical digestion of fats and lipophilic vitamins [45]. On top of that, even if the patient did not undergo surgery, pancreatic fibrosis due to the desmoplastic reaction with the loss of angiogenesis can occur [46].…”

Ping-Pong—Tumor and Host in Pancreatic Cancer Progression

“…PaCa cells can support angiogenesis (527-529) and microvessel density after PaCa resection correlates with recurrence and poor survival (530). Nonetheless, PaCa are mostly hypovascular and hypoxic, due to a dominance of negative angiogenesis modulators (531,532).…”