Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Clin Cancer Res. 2010 Jun 15;16(12):3130-40. doi: 10.1158/1078-0432.CCR-09-2846. Epub 2010 Jun 8.
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 anticancer 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.
刺猬（Hh）信号通路与多种人类肿瘤相关，早期针对该通路的拮抗剂的临床试验验证了 Hh 信号作为一个真正的抗癌靶点的作用。尽管这些结果令人鼓舞，但 Hh 信号通路在人类癌症中的基本生物学仍存在一些尚未阐明的问题。这些问题包括特定致癌事件对 Hh 信号转导的影响、在人类肿瘤中发生的 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性的最佳方法。癌症干细胞（CSC）假说可以解释许多临床现象，如不受控制的自我更新和转移性疾病的发展，在某种程度上，Hh 信号通路与所有这些过程都有关联。因此，Hh 信号通路抑制剂也可能代表首批在临床环境中正式检验 CSC 假说的药物之一。Hh 信号在人类癌症中的多样性表明，必须仔细考虑疾病特异性因素，以确定新型通路抑制剂的最佳使用方法。
