Han Jin-bin, Hua Yong-qiang, Chen Lian-yu, Liu Lu-ming
Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, China.
Zhong Xi Yi Jie He Xue Bao. 2012 Mar;10(3):256-63. doi: 10.3736/jcim20120303.
Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.
smoothened（SMO）是音猬因子同源（SHH）信号通路的成员。它作为patched-1（PTCH-1）和Gli之间的桥梁发挥关键作用。在各种恶性组织中均可检测到异常的SHH表达，且在胰腺癌干细胞中的表达明显更高。SHH信号与癌症干细胞的自我复制、肿瘤血管以及基质的形成密切相关。环杷明、GDC-0449等SMO拮抗剂显示出抑制SHH信号活性的潜力，并能阻止肿瘤的生长和转移。最近，一些SMO拮抗剂已进入I期临床试验，部分进入II期，同时，目前正在进行SMO拮抗剂治疗胰腺癌的I期或II期试验。作为经典的SMO拮抗剂，环杷明是从一种药用植物中提取的。也许未来研究人员能够从草药中确定更有效的靶向SMO的药物。
