Differential role of Hedgehog signaling in human pancreatic(patho-)physiology:An up to date review
作者机构：Institute of PathologyParacelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of SurgeryParacelsus Medical UniversitySalzburger Landeskliniken(SALK) Department of Internal Medicine IParacelsus Medical UniversitySalzburger Landeskliniken(SALK) Laboratory for Tumour Biology and Experimental Therapies(TREAT)Institute of Physiology and PathophysiologyParacelsus Medical University
出 版 物：《World Journal of Gastrointestinal Pathophysiology》 (世界胃肠病理生理学杂志（英文版）（电子版）)
年 卷 期：2016年第7卷第2期
页 面：199-210页
学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学]
主 题：Pancreatic cancer Hedgehog Pancreatitis Pancreas Development
摘 要：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.
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