ICBAS-Instituto de Ciências Biomédicas Abel Salazar, University of Porto, Porto, Portugal.
Mol Diagn Ther. 2014 Jun;18(3):285-91. doi: 10.1007/s40291-013-0081-0.
The incidence of melanoma has been continuously increasing in the last decades, and faster than any other cancers. Melanoma is the leading cause of death from skin disease. It is estimated that 76,690 Americans will be diagnosed with melanoma in 2013 and 9,480 will die from the disease. Molecular mechanisms underlying melanoma pathogenesis have been extensively studied and novel therapeutic weapons developed. BRAF and MEK pathways emerged as key players in this field. Recently, novel drugs such as vemurafenib, dabrafenib and trametinib were approved for treatment of advanced disease harbouring BRAF V600E and V600K mutations. In addition, an effective strategy to build upon the successes seen with dabrafenib and trametinib monotherapies has been to combine these agents (CombiDT), with the goal of further improving response rates and delaying resistance. Our review gives an overall point of view concerning BRAF and MEK pathways as well as the role of BRAF and MEK testing in directing the personalised treatment of patients with metastatic melanoma.
在过去几十年中，黑色素瘤的发病率一直在持续上升，而且上升速度比其他任何癌症都要快。黑色素瘤是皮肤疾病导致死亡的主要原因。据估计，2013 年将有 76690 名美国人被诊断患有黑色素瘤，其中 9480 人将死于该疾病。黑色素瘤发病机制的分子机制已得到广泛研究，并开发出了新的治疗武器。BRAF 和 MEK 通路已成为该领域的关键参与者。最近，批准了新型药物如 vemurafenib、dabrafenib 和 trametinib 用于治疗携带 BRAF V600E 和 V600K 突变的晚期疾病。此外，为了进一步提高反应率和延迟耐药性，建立在 dabrafenib 和 trametinib 单药治疗成功的基础上的有效策略是联合使用这些药物（CombiDT）。我们的综述全面介绍了 BRAF 和 MEK 通路以及 BRAF 和 MEK 检测在指导转移性黑色素瘤患者个体化治疗中的作用。
