Klieser Eckhard, Swierczynski Stefan, Mayr Christian, Jäger Tarkan, Schmidt Johanna, Neureiter Daniel, Kiesslich Tobias, Illig Romana
Eckhard Klieser, Johanna Schmidt, Daniel Neureiter, Romana Illig, Institute of Pathology, Paracelsus Medical University, Salzburger Landeskliniken (SALK), 5020 Salzburg, Austria.
World J Gastrointest Pathophysiol. 2016 May 15;7(2):199-210. doi: 10.4291/wjgp.v7.i2.199.
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.
自果蝇中发现刺猬（Hh）信号通路以来，在过去几十年里，我们对Hh在人类胚胎发育、炎症和癌症发生中的作用的了解有了显著增加。胰腺方面尤其如此，然而，迄今为止尚未取得真正的治疗突破。一般来说，Hh信号对于胰腺器官发生、发育和组织成熟至关重要。在急性胰腺炎中，Hh具有保护作用，而在慢性胰腺炎中，Hh与胰腺星状细胞相互作用，导致实质性纤维变性和萎缩，以及具有引发癌症发生潜能的不规则组织重塑。胰腺癌中Hh的体外和原位分析表明，Hh信号通路参与胰腺前体病变和导管腺癌的发展，包括与肿瘤微环境的关键相互作用。Hh信号通路成分特异性抑制剂的应用目前正处于正在进行的临床试验（1期和2期）阶段。此外，Hh信号通路抑制剂与已确立的化疗药物联合使用也可能是一种有前景的治疗方法。在本综述中，我们对Hh信号通路在胰腺发育、胰腺炎、胰腺癌发生和胰腺癌中的作用进行了结构化综述，并概述了目前关于Hh信号通路抑制剂和胰腺癌的临床试验情况。
