Department of Gastrointestinal Medical Oncology, Unit 426, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030-4009, USA.
Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
Cell Commun Signal. 2019 Nov 27;17(1):157. doi: 10.1186/s12964-019-0479-3.
Patients with advanced gastric cancer usually have a poor prognosis and limited therapeutic options. Overcoming this challenge requires novel targets and effective drugs. The Hedgehog (Hh) signaling pathway plays a crucial role in the development of the gastrointestinal tract and maintenance of the physiologic function of the stomach. Aberrantly activated Hh signaling is implicated in carcinogenesis as well as maintenance of cancer stem cells. Somatic mutations in the components of Hh signaling (PTCH1 and SMO) have been shown to be a major cause of basal cell carcinoma, and dozens of Hh inhibitors have been developed. To date, two inhibitors (GDC-0449 and LDE225) have been approved by the U.S. Food and Drug Administration to treat basal cell carcinoma and medulloblastoma. Here, we review the role of the Hh signaling in the carcinogenesis and progression of gastric cancer and summarize recent findings on Hh inhibitors in gastric cancer. Hedgehog signaling is often aberrantly activated and plays an important role during inflammation and carcinogenesis of gastric epithelial cells. Further study of the precise mechanisms of Hh signaling in this disease is needed for the validation of therapeutic targets and evaluation of the clinical utility of Hh inhibitors for gastric cancer.
患有晚期胃癌的患者通常预后较差，治疗选择有限。克服这一挑战需要新的靶点和有效的药物。Hedgehog（Hh）信号通路在胃肠道的发育和胃的生理功能维持中起着至关重要的作用。异常激活的 Hh 信号通路与肿瘤发生以及癌症干细胞的维持有关。Hh 信号通路成分（PTCH1 和 SMO）的体细胞突变已被证明是基底细胞癌的主要原因，并且已经开发了数十种 Hh 抑制剂。迄今为止，两种抑制剂（GDC-0449 和 LDE225）已被美国食品和药物管理局批准用于治疗基底细胞癌和髓母细胞瘤。在这里，我们综述了 Hh 信号在胃癌发生和进展中的作用，并总结了最近关于胃癌中 Hh 抑制剂的研究发现。Hh 信号通常异常激活，并在胃上皮细胞的炎症和癌变过程中发挥重要作用。需要进一步研究 Hh 信号在该疾病中的精确机制，以验证治疗靶点，并评估 Hh 抑制剂在胃癌中的临床应用价值。
