Pancreatic Biology Laboratory, Department of Surgery, Massachusetts General Hospital, Boston, MA, USA.
Surgery. 2012 Sep;152(3 Suppl 1):S19-32. doi: 10.1016/j.surg.2012.05.030. Epub 2012 Jul 6.
Developmental genes are known to regulate cell proliferation, migration, and differentiation; thus, it comes as no surprise that the misregulation of developmental genes plays an important role in the biology of human cancers. One such pathway that has received an increasing amount of attention for its function in carcinogenesis is the Hedgehog (Hh) pathway. Initially the domain of developmental biologists, the Hh pathway and one of its ligands, Sonic Hedgehog (Shh), have been shown to play an important role in body planning and organ development, particularly in the foregut endoderm. Their importance in human disease became known to cancer biologists when germline mutations that resulted in the unregulated activity of the Hh pathway were found to cause basal cell carcinoma and medulloblastoma. Since then, misexpression of the Hh pathway has been shown to play an important role in many other cancers, including those of the pancreas. In many institutions, investigators are targeting misexpression of the Hh pathway in clinical trials, but there is still much fundamental knowledge to be gained about this pathway that can shape its clinical utility. This review will outline the evolution of our understanding of this pathway as it relates to the pancreas, as well as how the Hh pathway came to be a high-priority target for treatment.
发育基因已知可调节细胞增殖、迁移和分化；因此，发育基因的失调在人类癌症的生物学中起着重要作用，这并不奇怪。在致癌作用方面，Hedgehog（Hh）途径是一条受到越来越多关注的途径。最初是发育生物学家的研究领域，Hh 途径及其配体 Sonic Hedgehog（Shh）已被证明在身体规划和器官发育中起着重要作用，特别是在前肠内胚层中。当发现导致 Hh 途径不受调节的基因突变会导致基底细胞癌和髓母细胞瘤时，癌症生物学家才开始了解其在人类疾病中的重要性。从那时起，Hh 途径的异常表达已被证明在许多其他癌症中发挥重要作用，包括胰腺癌。在许多机构中，研究人员正在临床试验中针对 Hh 途径的异常表达进行靶向治疗，但仍有许多关于该途径的基本认识有待提高，这将影响其临床应用。本文将概述我们对与胰腺相关的该途径的理解的演变，以及 Hh 途径如何成为治疗的高度优先目标。
