Pancreatic Cancer and Hedgehog Pathway Signaling: New Insights

While several aberrant signaling pathways have been attributed to the formation and progression of pancreatic cancer, there is mounting evidence for the increased role of the Hedgehog (Hh) pathway in multiple aspects of pancreatic tumor development. The Hh pathway is a signaling cascade that plays an important role in cell patterning of multiple tissues and organs, including the development of the gastrointestinal system. While normal pancreatic tissue exhibits little Hh pathway activity, patients with pancreatic adenocarcinoma show high levels of Hh pathway signaling in both the tumor epithelia and the surrounding mesenchyme. Several recent studies have focused on this paracrine activation of Hh signaling in the tumor microenvironment and have provided evidence for how activation of this pathway may play roles in mediating cellular proliferation, metastasis, and resistance to therapy. Together, these findings present new insights into how modulation of this pathway may allow us to target multiple aspects of pancreatic tumor biology.