Kappler Roland, von Schweinitz Dietrich
Department of Pediatric Surgery, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-University Munich, Munich, Germany.
Front Biosci (Schol Ed). 2012 Jan 1;4(1):277-86. doi: 10.2741/268.
Accumulated experimental evidence indicates that Hedgehog (Hh) signaling regulates cell proliferation and specification in a variety of organs during embryonic development. However, abnormal activation of this pathway in postnatal tissues has been linked to a large number of human cancers. With respect to the liver, it is known that Hh signaling not only influences bipotential precursor cells capable of pancreas and liver development, but is also implicated in the pathogenesis of liver tumors such as hepatoblastoma, hepatocellular and cholangiocellular carcinoma, if aberrantly activated. Blockade of Hh signaling by several specific inhibitors has been proven to successfully inhibit tumor growth of various Hh-associated cancers in vitro and in preclinical mouse models, and recent clinical data suggest that the implementation of novel anticancer therapeutics based on Hh interference into commonly accepted regimens are within reach. Thus, it is highly probable that Hh targeted therapies could be used for the treatment of Hh-dependent liver cancers in the future.
积累的实验证据表明，刺猬信号通路（Hh）在胚胎发育过程中调节多种器官中的细胞增殖和分化。然而，该信号通路在出生后组织中的异常激活与大量人类癌症相关。就肝脏而言，已知Hh信号不仅影响能够发育成胰腺和肝脏的双能前体细胞，而且如果异常激活，还与肝母细胞瘤、肝细胞癌和胆管细胞癌等肝脏肿瘤的发病机制有关。几种特异性抑制剂对Hh信号通路的阻断已被证明能在体外和临床前小鼠模型中成功抑制各种与Hh相关癌症的肿瘤生长，最近的临床数据表明，将基于Hh干扰的新型抗癌疗法纳入常用治疗方案已指日可待。因此，Hh靶向治疗很有可能在未来用于治疗依赖Hh的肝癌。
