文章：

从基因到药物：黑色素瘤的靶向策略

From genes to drugs: targeted strategies for melanoma

原文发布日期：2012-04-05

DOI: 10.1038/nrc3218

类型: Review Article

开放获取: 否

要点：

1. Oncogenic mutations in melanoma are increasingly well categorized and are not stand-alone events.
2. Several highly recurrent oncogenic mutations in melanoma occur within known signalling pathways. The most common of these is BRAF-V600E, which occurs in approximately 50% of melanomas.
3. Targeted therapies seek to inhibit functionally causative oncoproteins and have shown substantial promise in recent months.
4. Successful targeting of the BRAF-V600E or mutant KIT kinases has produced significant clinical responses in patients with advanced melanoma harbouring those mutations.
5. Targeted inhibition of the immune tolerance checkpoint with a blocking antibody approach has produced significant clinical responses in patients with advanced melanoma.
6. Permanent control of advanced melanoma remains uncommon for suppression of signalling or immune checkpoint targets. Improved strategies focus both on the development of new targeted therapeutics and on the analysis of combinations of these treatments.

要点翻译：

1. 黑色素瘤中的致癌突变已日益明确，并非孤立事件。
2. 多个高频复发的致癌突变出现在已知信号通路中。其中最常见的是BRAF-V600E突变，约存在于50%的黑色素瘤病例。
3. 靶向治疗旨在抑制功能性致病癌蛋白，近月以来展现出显著前景。
4. 对BRAF-V600E或突变KIT激酶的成功靶向治疗，已在携带这些突变的晚期黑色素瘤患者中产生显著临床应答。
5. 通过阻断抗体方法对免疫耐受检查点进行靶向抑制，在晚期黑色素瘤患者中引发了重要临床反应。
6. 针对信号通路或免疫检查点的抑制治疗，仍鲜能实现晚期黑色素瘤的长期控制。改进策略既聚焦于开发新型靶向药物，也着力于分析这些治疗的组合方案。

英文摘要：

The past decade has revealed that melanoma is comprised of multiple subclasses that can be categorized on the basis of key features, including the clinical stage of disease, the oncogenic molecular 'drivers', the anatomical location or the behaviour of the primary lesion and the expression of specific biomarkers. Although exercises in subclassification are not new in oncology, progress in this area has produced both conceptual and clinical breakthroughs, which, for melanoma, are unprecedented in the modern history of the disease. This Review focuses on these recent striking advances in the strategy of molecularly targeted approaches to the therapy of melanoma in humans.

摘要翻译： 

过去十年揭示出，黑色素瘤包含多个亚类，可依据关键特征进行分类，包括疾病的临床分期、致癌分子“驱动因素”、解剖部位、原发灶行为以及特定生物标志物的表达。尽管肿瘤亚类划分在肿瘤学中并非新概念，但此领域的进展带来了概念与临床的双重突破，对黑色素瘤而言，这在现代疾病史上尚属首次。本文综述重点介绍了人类黑色素瘤分子靶向治疗策略中这些近期引人注目的进展。

原文链接：

From genes to drugs: targeted strategies for melanoma