Exp Dermatol. 2011 Dec;20(12):1030-2. doi: 10.1111/j.1600-0625.2011.01385.x.
Selection for targeted therapies in melanoma is currently based on the search for mutations in selected genes. We aimed at evaluating the interest of signalling and chemosensitivity studies in addition to genotyping for assessing the best suitable treatment in an individual patient. We extracted genomic DNA and melanoma cells from tumor tissue of a skin metastasis of a 17-year-old woman with stage IV melanoma progressing despite three successive lines of treatment. Despite the absence of mutation in BRAF, NRAS cKIT, the MAPK pathway was activated and a significant response to sorafenib, a mitogen-activated protein kinase (MAPK)/RAF inhibitor, was found in signalling and chemosensitivity assays. A treatment combining sorafenib and dacarbazine produced a partial response for 9 months, with marked necrosis in some lesions. Chemosensitivity assays and signalling pathway studies could be of great value in addition to genotyping for assessing the most appropriate treatment in melanoma.
目前，黑色素瘤的靶向治疗选择基于对选定基因的突变检测。我们旨在评估信号通路和化疗敏感性研究以及基因分型的意义，以评估每位患者的最佳治疗方案。我们从一名 17 岁女性的皮肤转移黑色素瘤的肿瘤组织中提取了基因组 DNA 和黑色素瘤细胞，该患者尽管接受了三线治疗，但仍出现进展。尽管 BRAF 和 NRAS cKIT 没有突变，但 MAPK 通路被激活，并且在信号通路和化疗敏感性检测中发现索拉非尼（一种丝裂原活化蛋白激酶 (MAPK)/RAF 抑制剂）有显著的反应。索拉非尼联合达卡巴嗪的治疗方案产生了 9 个月的部分缓解，一些病变出现明显坏死。除了基因分型外，化疗敏感性检测和信号通路研究在评估黑色素瘤的最佳治疗方案方面可能具有重要价值。
