Haluska Frank G, Ibrahim Nageatte
Cancer Center and Division of Hematology/Oncology, Tufts New England Medical Center, Boston, MA 02111, USA.
Curr Oncol Rep. 2006 Sep;8(5):400-5. doi: 10.1007/s11912-006-0065-x.
Recent progress in our understanding of the genetic alterations that occur in the pathogenesis of melanoma provides exciting opportunities for therapy. The most important signaling pathways in melanoma lie downstream of NRAS: the RAS-BRAF-MAPK pathway. A great deal of attention has been focused on the high mutation rate in the BRAF oncogene, which approaches 60%, because BRAF itself is an appealing drug substrate and because of the central contribution of BRAF function to melanoma development that the mutation rate signifies. Agents that specifically target BRAF, such as sorafenib, as well as new molecules that function both upstream and downstream of BRAF, are being actively investigated.
我们对黑色素瘤发病机制中发生的基因改变的最新认识进展为治疗提供了令人兴奋的机会。黑色素瘤中最重要的信号通路位于NRAS下游：RAS-BRAF-MAPK通路。大量关注集中在BRAF癌基因的高突变率上，该突变率接近60%，这是因为BRAF本身是一种有吸引力的药物作用底物，也因为该突变率所表明的BRAF功能对黑色素瘤发展的核心作用。正在积极研究特异性靶向BRAF的药物，如索拉非尼，以及在BRAF上下游均起作用的新分子。
