文章：

基底细胞癌：刺猬的攻击

Basal cell carcinomas: attack of the hedgehog

原文发布日期：2008-10-01

DOI: 10.1038/nrc2503

类型: Review Article

开放获取: 否

要点：

1. Basal cell carcinomas (BCCs) are keratinocyte tumours that resemble the basal layer of the epidermis, and are the most commonly diagnosed human cancer among persons of European ancestry.
2. Despite this high frequency, the death rate is extraordinarily low, a reflection perhaps of the excellent care provided by physicians and of their vanishingly rare propensity to metastasize.
3. The vast majority of BCCs occur sporadically, but patients with the rare heritable disorder basal cell nevus syndrome (BCNS) have a marked susceptibility to developing BCCs.
4. Family based linkage studies of kindreds with BCNS identified the patched 1 (PTCH1) gene, an inhibitor of the hedgehog signalling pathway, as being mutated in these patients. p53 is also mutated in some patients with sporadic BCCs.
5. Downstream signalling pathways that are deregulated in patients with BCCs are currently being investigated.
6. Surgery is curative for most patients with BCCs. However, for those few that develop locally advanced or metastatic BCC, for which there is currently no effective treatment, Phase I clinical trials with inhibitors of the hedgehog signalling pathway have produced promising results.

要点翻译：

1. 癌症干细胞（CSC）假说是一个颇具吸引力的模型，用以解释实体瘤中常见的功能异质性现象。该假说提出肿瘤内部细胞存在层级结构，其中具有干细胞特性的亚群负责维持肿瘤的生长。
2. CSC的首个证据来自急性髓系白血病。目前通过前瞻性分离肿瘤细胞的移植研究，越来越多证据表明多种实体瘤（包括小鼠和人类）中存在CSC。
3. 实体瘤中CSC的出现频率存在显著差异，这既反映了生物学变异，也涉及技术问题。技术问题包括实体瘤细胞分馏的纯度、对更明确标志物的需求，以及异种移植相关的挑战。最终需要通过“细胞标记”技术在克隆水平研究CSC及其潜在异质性。
4. 并非所有实体瘤都遵循CSC异质性模型。有些肿瘤可能符合克隆进化模型，即由占主导地位的增殖细胞群驱动肿瘤发生。
5. 可能存在转移性CSC，其特性与原发CSC不同。
6. CSC概念具有重要临床意义：研究表明CSC对化疗和放疗具有更强耐药性。
7. 最新研究（主要针对造血系统恶性肿瘤）表明，可以在不损伤正常干细胞功能的前提下选择性靶向CSC。

英文摘要：

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.

摘要翻译： 

基底细胞癌（BCC）在约12年前基本上还是一个分子“黑箱”，直到在少数极易发生BCC的患者中发现了一种遗传缺陷，指出异常的Hedgehog信号通路是这些肿瘤形成的关键缺陷。这一发现极大地促进了我们对于BCC致癌机制的理解，并突显了这一发育通路在成年期异常激活时的致癌作用。重要的是，一项Hedgehog抑制剂首次用于人体的I期试验已显示出在阻止甚至逆转这些肿瘤生长方面的实质性进展。

原文链接：

Basal cell carcinomas: attack of the hedgehog