Kee Damien, McArthur Grant
Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia; Department of Pathology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia.
Division of Cancer Medicine and Research, Peter MacCallum Cancer Centre, St Andrews Place, East Melbourne, Victoria 3002, Australia; Department of Pathology, University of Melbourne, Grattan Street, Parkville, Victoria 3010, Australia; Department of Medicine, St Vincent Hospital, University of Melbourne, Victoria Parade, Fitzroy, Victoria 3065, Australia.
Hematol Oncol Clin North Am. 2014 Jun;28(3):491-505. doi: 10.1016/j.hoc.2014.02.003. Epub 2014 Apr 3.
Melanoma is resistant to cytotoxic therapy, and treatment options for advanced disease have been limited historically. However, improved understanding of melanoma driver mutations, particularly those involving the mitogen-activated protein kinase pathway, has led to the development of targeted therapies that are effective in this previously treatment-refractory disease. In cutaneous melanomas with BRAF V600 mutations the selective RAF inhibitors, vemurafenib and dabrafenib, and the MEK inhibitor, trametinib, have demonstrated survival benefits. Early signals of efficacy have also been demonstrated with MEK inhibitors in melanomas with NRAS mutations, and KIT inhibitors offer promise in melanomas driven through activation of their target receptor.
黑色素瘤对细胞毒性疗法具有抗性，并且从历史上看，晚期疾病的治疗选择一直有限。然而，对黑色素瘤驱动基因突变的深入了解，尤其是那些涉及丝裂原活化蛋白激酶途径的突变，已促使开发出在这种先前难治性疾病中有效的靶向疗法。在具有BRAF V600突变的皮肤黑色素瘤中，选择性RAF抑制剂维莫非尼和达拉非尼以及MEK抑制剂曲美替尼已显示出生存获益。在具有NRAS突变的黑色素瘤中，MEK抑制剂也已显示出早期疗效信号，并且KIT抑制剂在通过其靶受体激活驱动的黑色素瘤中具有前景。
