title: Differential role of Hedgehog signaling in human pancreatic (patho-) physiology: An up to date review.
abstract: Since the discovery of the Hedgehog (Hh) pathway in drosophila melanogaster, our knowledge of the role of Hh in embryonic development, inflammation, and cancerogenesis in humans has dramatically increased over the last decades. This is the case especially concerning the pancreas, however, real therapeutic breakthroughs are missing until now. In general, Hh signaling is essential for pancreatic organogenesis, development, and tissue maturation. In the case of acute pancreatitis, Hh has a protective role, whereas in chronic pancreatitis, Hh interacts with pancreatic stellate cells, leading to destructive parenchym fibrosis and atrophy, as well as to irregular tissue remodeling with potency of initiating cancerogenesis. In vitro and in situ analysis of Hh in pancreatic cancer revealed that the Hh pathway participates in the development of pancreatic precursor lesions and ductal adenocarcinoma including critical interactions with the tumor microenvironment. The application of specific inhibitors of components of the Hh pathway is currently subject of ongoing clinical trials (phases 1 and 2). Furthermore, a combination of Hh pathway inhibitors and established chemotherapeutic drugs could also represent a promising therapeutic approach. In this review, we give a structured survey of the role of the Hh pathway in pancreatic development, pancreatitis, pancreatic carcinogenesis and pancreatic cancer as well as an overview of current clinical trials concerning Hh pathway inhibitors and pancreas cancer.
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Klieser
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Swierczynski
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Mayr
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Tarkan
authors.initials: T
authors.lastname: Jäger
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Johanna
authors.initials: J
authors.lastname: Schmidt
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.affiliation: Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
authors.forename: Romana
authors.initials: R
authors.lastname: Illig
keywords: Development; Hedgehog; Pancreas; Pancreatic cancer; Pancreatitis