Basal cell carcinomas: attack of the hedgehog.
Basal cell carcinomas: attack of the hedgehog.
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DOI：
10.1038/nrc2503
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发表时间：
2008-10
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中科院分区：
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大约12年前，基底细胞癌（BCC）在本质上还是一个分子学上的“黑匣子”。当时，在一小部分极易患基底细胞癌的患者中发现了一种基因缺陷，这表明异常的刺猬信号通路是导致这些肿瘤形成的关键缺陷。这一发现极大地增进了我们对基底细胞癌致癌作用的理解，并凸显了这种在发育过程中起作用的通路在成年期异常激活时的致癌作用。重要的是，一项针对刺猬信号通路抑制剂的1期首次人体试验表明，在阻止甚至逆转这些肿瘤的生长方面取得了实质性进展。
Basal cell carcinomas (BCCs) were essentially a molecular ‘black box’ until some 12 years ago, when identification of a genetic flaw in a rare subset of patients who have a great propensity to develop BCCs pointed to aberrant Hedgehog signalling as the pivotal defect leading to formation of these tumours. This discovery has facilitated a remarkable increase in our understanding of BCC carcinogenesis and has highlighted the carcinogenic role of this developmental pathway when aberrantly activated in adulthood. Importantly, a phase 1 first-in-human trial of a Hedgehog inhibitor has shown real progress in halting and even reversing the growth of these tumours.