Hedgehog (Hh) signaling is a principal component of the morphogenetic code best known to direct pattern formation during embryogenesis. The Hh pathway remains active in adulthood however where it guides tissue regeneration and remodeling and Hh production in the niche plays an important role in maintaining stem cell compartment size. Deregulated Hh signaling activity is associated, depending on the context, with both cancer initiation and progression. Interestingly, the Hh pathway is remarkably druggable, raising hopes that inhibition of the pathway could support anticancer therapy. Indeed, a large body of preclinical data supports such an action, but promising clinical data are still limited to basal cell carcinoma (BSC) and medulloblastoma. Nevertheless cancer resistance against Hh targeting has already emerged as a major problem. Here we shall review the current situation with respect to targeting the Hh pathway in cancer in general and in chemotolerance in particular with a focus on the problems associated with the emergence of tumors resistant to treatment with inhibitors targeting the Hh receptor Smoothened (SMO).

中文翻译：

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靶向刺猬信号并了解对刺猬途径抑制剂治疗的难治性反应。

刺猬（Hh）信号是形态发生密码的主要组成部分，众所周知，它在胚胎发生过程中指导模式形成。Hh途径在成年期仍然保持活跃，但是它指导组织再生和重塑，而利基族中的Hh产生在维持干细胞区室大小中起重要作用。根据上下文，Hh信号转导活性的失调与癌症的发生和发展有关。有趣的是，Hh途径具有显着的药物作用，人们希望该途径的抑制能够支持抗癌治疗。确实，大量的临床前数据支持这种作用，但是有希望的临床数据仍然仅限于基底细胞癌（BSC）和髓母细胞瘤。然而，针对Hh靶向的抗癌性已经出现为主要问题。