Charles J, Martel C, de Fraipont F, Leccia M-T, Robert C, Busser B
Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France; Dermatologie, CHU de Grenoble, CS 10217, 38043 Grenoble cedex 9, France.
Centre de recherche Inserm/UJF U823, institut Albert-Bonniot, BP 170, 38042 Grenoble cedex 9, France.
Ann Dermatol Venereol. 2014 Nov;141(11):671-81. doi: 10.1016/j.annder.2014.06.021. Epub 2014 Aug 7.
In patients with melanoma positive for the BRAF V600 mutation, clinical response to specific BRAF inhibitors is usually rapid and striking, with significant benefits in terms of progression-free survival and overall survival. However, resistance to treatment almost invariably arises, typically within a median timeframe of 6 months. Indeed, very few patients exhibit long-lasting response to these targeted therapies.
It is essential to better understand the mechanisms of resistance to targeted anti-BRAF therapies in order to increase both response rates and the duration of clinical response to treatment. This literature review describes the signaling pathways involving BRAF and presents recent data from clinical trials with these molecules. Furthermore, we aim to describe the main resistance mechanisms linked with targeted anti-BRAF therapies.
The keywords (resistance, BRAF, melanoma, targeted therapy, vemurafenib, and dabrafenib) were used to extract relevant articles in the Medline/Pubmed database published before 31 January 2014.
Improved knowledge and understanding of the mechanisms of resistance to targeted anti-BRAF therapies should enable the development of new therapeutic strategies in order to overcome such resistance and allow more significant and sustained response rates to be achieved among melanoma patients.
在BRAF V600突变阳性的黑色素瘤患者中，对特定BRAF抑制剂的临床反应通常迅速且显著，在无进展生存期和总生存期方面有显著益处。然而，几乎总会出现对治疗的耐药性，通常在中位6个月的时间内出现。事实上，很少有患者对这些靶向治疗表现出持久反应。
为了提高反应率和治疗的临床反应持续时间，更好地理解对靶向抗BRAF治疗的耐药机制至关重要。这篇文献综述描述了涉及BRAF的信号通路，并展示了这些分子的近期临床试验数据。此外，我们旨在描述与靶向抗BRAF治疗相关的主要耐药机制。
使用关键词（耐药性、BRAF、黑色素瘤、靶向治疗、维莫非尼、达拉非尼）在Medline/Pubmed数据库中提取2014年1月31日前发表的相关文章。
对靶向抗BRAF治疗耐药机制的进一步了解和认识应有助于开发新的治疗策略，以克服这种耐药性，并使黑色素瘤患者获得更高且持续的反应率。
