Advances in Smoothened-targeting therapies for pancreatic cancer: implication for drug discovery from herbal medicines.
Advances in Smoothened-targeting therapies for pancreatic cancer: implication for drug discovery from herbal medicines.
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DOI：
10.3736/jcim20120303
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发表时间：
2012-03-01
期刊：
影响因子：
--
通讯作者：
Liu, Lu-ming
中科院分区：
文献类型：
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作者：
Han, Jin-bin;Hua, Yong-qiang;Liu, Lu-ming
Smoothened（SMO）是音刺猬同源性（SHH）信号通路的成员。它作为patched-1（PTCH-1）和Gli之间的桥梁发挥着关键作用。SHH在多种恶性肿瘤组织中均有异常表达，在胰腺癌干细胞中表达明显增高。SHH信号与肿瘤干细胞的自我复制、肿瘤血管和基质的形成密切相关。SMO拮抗剂如环巴胺、GDC-0449等具有抑制SHH信号通路活性、抑制肿瘤生长和转移的作用。近年来，SMO拮抗剂的研究已进入I期临床试验阶段，部分药物已进入II期临床试验阶段，目前正在进行SMO拮抗剂治疗胰腺癌的I期或II期临床试验。环巴胺是从药用植物中提取的经典SMO拮抗剂。也许研究人员将来能够从草药中确定更有效的SMO靶向药物。
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.