Dierks Christine
Department of Hematology and Oncology, Freiburg University Medical Center, Hugstetterstrasse. 55, 79106, Freiburg, Germany.
Recent Results Cancer Res. 2010;184:235-8. doi: 10.1007/978-3-642-01222-8_17.
Hedgehog signaling is activated in a variety of solid tumors and hematologic malignancies by point mutations in hedgehog pathway members or autocrine or paracrine ligand secretion. Several hedgehog inhibitors were developed to block hedgehog pathway activity on the level of the activating receptor, Smoothened (Smo). GDC-0449 is the first systemic Smo-inhibitor entering clinical trials. It was successfully tested in a phase-I clinical trial demonstrating good pharmacodynamic (PD) and pharmacokinetic (PK) properties and showing objective response and clinical benefit in several patients with basal cell carcinoma.
通过刺猬信号通路成员的点突变或自分泌或旁分泌配体分泌，刺猬信号在多种实体瘤和血液系统恶性肿瘤中被激活。已开发出几种刺猬信号抑制剂，以在激活受体 smoothened（Smo）水平阻断刺猬信号通路活性。GDC-0449 是首个进入临床试验的全身性 Smo 抑制剂。它在一项 I 期临床试验中成功进行了测试，显示出良好的药效学（PD）和药代动力学（PK）特性，并在数例基底细胞癌患者中显示出客观反应和临床获益。
