Pancreatic Cancer - The Role of Hypoxia

Abstract

Pancreatic cancer has very poor prognosis and has a very low five-year survival rate of the order of 5%. This is so because of the lack of major clinical symptoms and reliable detection markers. Recently, it has been realized that hypoxia is one of the major contributors to tumor growth, malignancy, invasion, propagation, metastasis, and resistance to therapy in several solid tumors including the pancreatic cancer. Understandably, it has gained even more importance in pancreatic cancer and is considered as the primary target for its therapy in the recent times since it has been identified as the major determinant of cancer malignancy. This importance is due to the reason that hypoxia triggers several reactions in the process of tumor progression and metastasis. The main signaling mechanism is through the Hypoxia-Inducible Factors (HIFs) that are mostly activated by the oncogenes and the tumor suppressor genes. This review is an attempt to present a comprehensive picture of the disease and the role of hypoxia in its progression. The review will discuss the various mechanisms of action of hypoxia through the stroma and the microenvironment in the invasion and metastasis of pancreatic cancer. It will also very briefly summarize the means of therapy of pancreatic cancer by targeting the hypoxia.

Keywords

Pancreatic cancer, HIF, PDAC, Hypoxia, Stroma, Microenvironment

Abbreviations

PDA: Pancreatic Ductal Adenocarcinoma; PanIN: Pancreatic Intraepithelial Neoplasia; HIF: Hypoxia-Inducible Factor