Atwood Scott X, Whitson Ramon J, Oro Anthony E
Program in Epithelial Biology, Stanford University School of Medicine, Stanford, California 94305.
Cold Spring Harb Perspect Med. 2014 Jul 1;4(7):a013581. doi: 10.1101/cshperspect.a013581.
Basal cell carcinomas (BCCs) are very common epithelial cancers that depend on the Hedgehog pathway for tumor growth. Traditional therapies such as surgical excision are effective for most patients with sporadic BCC; however, better treatment options are needed for cosmetically sensitive or advanced and metastatic BCC. The first approved Hedgehog antagonist targeting the membrane receptor Smoothened, vismodegib, shows remarkable effectiveness on both syndromic and nonsyndromic BCCs. However, drug-resistant tumors frequently develop, illustrating the need for the development of next-generation Hedgehog antagonists targeting pathway components downstream from Smoothened. In this article, we will summarize available BCC treatment options and discuss the development of next-generation antagonists.
基底细胞癌（BCCs）是非常常见的上皮性癌症，其肿瘤生长依赖于Hedgehog信号通路。传统疗法如手术切除对大多数散发性基底细胞癌患者有效；然而，对于美容敏感型或晚期及转移性基底细胞癌，需要更好的治疗选择。首个获批的靶向膜受体Smoothened的Hedgehog拮抗剂维莫德吉，对综合征性和非综合征性基底细胞癌均显示出显著疗效。然而，耐药肿瘤经常出现，这表明需要开发针对Smoothened下游通路成分的新一代Hedgehog拮抗剂。在本文中，我们将总结现有的基底细胞癌治疗选择，并讨论新一代拮抗剂的研发情况。
