Division of Medical Oncology, Duke University Medical Center, DUMC 3476, Durham, NC, 27710, USA,
Curr Oncol Rep. 2013 Oct;15(5):473-82. doi: 10.1007/s11912-013-0336-2.
The RAS-RAF-MEK-ERK pathway is considered to be the most important signal transduction pathway in melanoma, and alterations in this pathway via various genetic mutations, such as BRAF and NRAS mutations, are known to be important drivers of melanomagenesis. As MEK is an essential intermediary kinase protein within this pathway, inhibition of MEK has been of a great interest as a molecular target therapy in melanoma. In fact, trametinib, a selective MEK inhibitor, has been shown to have a survival benefit over cytotoxic chemotherapy in patients with V600 BRAF-mutant metastatic melanoma, leading to the FDA approval for this patient population. MEK inhibitors may also be useful in treatment of advanced melanoma harboring other genetic mutations, such as NRAS and GNAQ/GNA11 mutations. Here, we review and discuss the preclinical and clinical data regarding MEK inhibitors and their role in the treatment of advanced melanoma.
RAS-RAF-MEK-ERK 通路被认为是黑色素瘤中最重要的信号转导通路，该通路中的各种基因突变，如 BRAF 和 NRAS 突变，被认为是黑色素瘤发生的重要驱动因素。由于 MEK 是该通路中的关键中间激酶蛋白，因此抑制 MEK 作为黑色素瘤的分子靶向治疗已引起极大关注。事实上，选择性 MEK 抑制剂曲美替尼已被证明在 V600 BRAF 突变转移性黑色素瘤患者中比细胞毒性化疗更具生存获益，这促使 FDA 批准该药物用于此类患者人群。MEK 抑制剂在治疗携带其他基因突变（如 NRAS 和 GNAQ/GNA11 突变）的晚期黑色素瘤中也可能有用。在这里，我们综述并讨论了有关 MEK 抑制剂的临床前和临床数据及其在晚期黑色素瘤治疗中的作用。
