Targeting Hedgehog--a cancer stem cell pathway.
Targeting Hedgehog--a cancer stem cell pathway.
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DOI：
10.1158/1078-0432.ccr-09-2846
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发表时间：
2010-06-15
期刊：
影响因子：
--
通讯作者：
Matsui W
中科院分区：
文献类型：
--
作者：
Merchant AA;Matsui W
Hedgehog(HH)通路与多种人类肿瘤有关，早期使用通路拮抗剂的临床试验已经证实HH信号是一个真正的抗癌靶点。尽管有这些令人鼓舞的结果，围绕人类癌症中HH途径的基础生物学的几个问题仍然不清楚。这些包括特定致癌事件对HH信号转导的影响，人类肿瘤内HH信号的确切模式(即自分泌或旁分泌)，以及在临床环境中抑制异常通路活动的最佳方法。肿瘤干细胞(CSC)假说可以解释许多临床现象，如无节制的自我更新和转移疾病的发展，在某种程度上，HH信号通路参与了所有这些过程。因此，HH途径抑制剂也可能代表着在临床环境中正式检验CSC假说的一些首批药物。人类癌症中HH信号的多样性表明，必须仔细考虑疾病特异性因素，以确定新途径抑制剂的最佳使用。
The Hedgehog (Hh) pathway has been implicated in a wide variety of human tumors, and early clinical trials with pathway antagonists have validated Hh signaling as a bona fide anti-cancer target. Despite these encouraging results, several issues surrounding the basic biology of the Hh pathway in human cancers remain unclear. These include the influence of specific oncogenic events on Hh signal transduction, the precise mode of Hh signaling (i.e., autocrine or paracrine) that occurs within human tumors, and the best means to inhibit aberrant pathway activity in the clinical setting. The cancer stem cell (CSC) hypothesis may explain a number of clinical phenomena, such as unchecked self-renewal and the development of metastatic disease, and to some extent, the Hh signaling pathway has been implicated in all of these processes. Therefore, Hh pathway inhibitors may also represent some of the first agents to formally examine the CSC hypothesis in the clinical setting. The diverse nature of Hh signaling in human cancers suggests that disease-specific factors must be carefully considered to identify the optimal use of novel pathway inhibitors.