Sint-Augustinus Hospital, Oosterveldlaan 24, Antwerp, Belgium.
Future Oncol. 2012 Aug;8(8):915-28. doi: 10.2217/fon.12.82.
Hedgehog pathway signaling is important for embryonic development; however, inappropriate reactivation of this pathway in adults has been linked to several forms of cancer. Vismodegib (Erivedge™), a first-in-class hedgehog pathway inhibitor, blocks the pathway by inhibiting the activity of the signaling protein SMO. Preclinical studies have provided promising indications of potential tumor-reducing activity in several cancers. Thus far, clinical pharmacology and Phase I studies have demonstrated the unique pharmacokinetic profile of vismodegib, its efficacy in certain types of tumors and a generally tolerable adverse-event profile. A pivotal Phase II clinical trial confirmed the favorable benefit:risk profile of vismodegib in advanced basal cell carcinoma.
hedgehog 通路信号转导对胚胎发育很重要；然而，该通路在成人中的异常激活与几种癌症有关。维莫德吉（ErivedgeTM）是一种首创的 hedgehog 通路抑制剂，通过抑制信号蛋白 SMO 的活性来阻断该通路。临床前研究为几种癌症的潜在肿瘤缩小活性提供了有希望的迹象。到目前为止，临床药理学和 I 期研究已经证明了维莫德吉独特的药代动力学特征、其在某些类型肿瘤中的疗效以及通常可耐受的不良事件特征。一项关键的 II 期临床试验证实了维莫德吉在晚期基底细胞癌中的良好获益风险比。
