Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Crit Rev Oncol Hematol. 2014 Oct;92(1):25-37. doi: 10.1016/j.critrevonc.2014.05.002. Epub 2014 May 12.
Barrett's metaplasia of the esophagus (BE) is the precursor lesion of esophageal adenocarcinoma (EAC), a deadly disease with a 5-year overall survival of less than 20%. The molecular mechanisms of BE development and its transformation to EAC are poorly understood and current surveillance and treatment strategies are of limited efficacy. Increasing evidence suggests that aberrant signaling through pathways active in the embryological development of the esophagus contributes to BE development and progression to EAC. We discuss the role that the Bone morphogenetic protein, Hedgehog, Wingless-Type MMTV Integration Site Family (WNT) and Retinoic acid signaling pathways play during embryological development of the esophagus and their contribution to BE development and malignant transformation. Modulation of these pathways provides new therapeutic opportunities. By integrating findings in developmental biology with those from translational research and clinical trials, this review provides a platform for future studies aimed at improving current management of BE and EAC.
食管的 Barrett 化生（BE）是食管腺癌（EAC）的前体病变，这种致命疾病的 5 年总生存率不到 20%。BE 发展及其向 EAC 转化的分子机制尚不清楚，目前的监测和治疗策略效果有限。越来越多的证据表明，胚胎发育过程中异常信号通路的活性与 BE 的发展和向 EAC 的进展有关。我们讨论了骨形态发生蛋白、Hedgehog、Wingless-Type MMTV 整合位点家族（WNT）和视黄酸信号通路在食管胚胎发育过程中的作用及其对 BE 发展和恶性转化的贡献。这些途径的调节为提供了新的治疗机会。通过将发育生物学中的发现与转化研究和临床试验的结果相结合，本综述为未来旨在改善 BE 和 EAC 现有管理的研究提供了一个平台。
