Gençler Bilgen, Gönül Müzeyyen
Department of Dermatology, Ministry of Health Diskapi Yildirim Beyazit Education and Research Hospital, 06110 Ankara, Turkey.
Dermatol Res Pract. 2016;2016:5361569. doi: 10.1155/2016/5361569. Epub 2016 Mar 3.
The incidence of melanoma has recently been increasing. BRAF mutations have been found in 40-60% of melanomas. The increased activity of BRAF V600E leads to the activation of downstream signaling through the mitogen-activated protein kinase (MAPK) pathway, which plays a key role as a regulator of cell growth, differentiation, and survival. The use of BRAF inhibitors in metastatic melanoma with BRAF mutation ensures clinical improvement of the disease. Vemurafenib and dabrafenib are two selective BRAF inhibitors approved by the Food and Drug Administration (FDA). Both drugs are well tolerated and successfully used in clinical practice. However, some adverse reactions have been reported in patients in the course of treatment. Cutaneous side effects are the most common adverse events among them with a broad spectrum. Both the case reports and several original clinical trials reported cutaneous reactions during the treatment with BRAF inhibitors. In this review, the common cutaneous side effects of BRAF inhibitors in the treatment of metastatic melanoma with BRAF V600E mutation were reviewed.
黑色素瘤的发病率最近一直在上升。在40%-60%的黑色素瘤中发现了BRAF突变。BRAF V600E活性的增加通过丝裂原活化蛋白激酶(MAPK)途径导致下游信号的激活,该途径作为细胞生长、分化和存活的调节因子发挥关键作用。在伴有BRAF突变的转移性黑色素瘤中使用BRAF抑制剂可确保疾病的临床改善。维莫非尼和达拉非尼是两种经美国食品药品监督管理局(FDA)批准的选择性BRAF抑制剂。这两种药物耐受性良好,并成功应用于临床实践。然而,在治疗过程中,患者出现了一些不良反应。皮肤副作用是其中最常见的不良事件,范围广泛。病例报告和多项原始临床试验均报道了BRAF抑制剂治疗期间的皮肤反应。在本综述中,对BRAF抑制剂治疗伴有BRAF V600E突变的转移性黑色素瘤时常见的皮肤副作用进行了综述。