Resolving the HIF paradox in pancreatic cancer.
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is currently the third leading cause of cancer-related deaths and has a 5-year survival rate of less than 10%, far below the ~70% national average for all cancers. This poor prognosis is driven by an extreme resistance to nearly all known cancer treatments, which has long been attributed to hypoxia driven interactions between tumor cells and the supporting stromal microenvironment. The cellular response to hypoxia is driven by the transcription factors known as the hypoxia inducible factors (HIFs), which have been hypothesized to play a role in the pathobiology of PDAC as well as a potential therapeutic target based on years of cell culture data. Attempts to validate the oncogenic role of HIF in PDAC through rigorous spontaneous tumor models have paradoxically shown that the HIFs may act as a tumor suppressor in epithelial cells. Here, we seek to resolve this paradox by discussing the roles of HIFs both in cancer cells and the supporting microenvironment and place them into context of current model systems that could be used to interrogate these interactions. We suggest that HIF may exert its oncogenic influences by modulating the form and function of the stroma rather than direct effects...Continue Reading
References
Why is the partial oxygen pressure of human tissues a crucial parameter? Small molecules and hypoxia
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Carcinoma, Ductal
Ductal carcinoma is a malignant neoplasm involving the ductal systems of any of a number of organs, such as the mammary glands, pancreas, prostate or lacrimal gland. Discover the latest research on ductal carcinoma here.