Komatsubara Kimberly M, Manson Daniel K, Carvajal Richard D
Division of Hematology/Oncology, Columbia University Medical Center, New York, NY, USA.
Future Oncol. 2016 Jun;12(11):1331-44. doi: 10.2217/fon-2015-0075. Epub 2016 Apr 5.
Uveal melanoma is a rare but aggressive subtype of melanoma. Nearly 50% of patients will develop metastatic disease despite primary enucleation or radiation therapy. There is currently no standard of care therapy for metastatic uveal melanoma, and no therapy that has been shown to prolong overall survival. Uveal melanoma is characterized by activation of signaling pathways including the MAPK pathway and the PI3K/AKT pathway, among others, via mutations in the G-α-proteins GNAQ and GNA11. MEK inhibition with selumetinib has been evaluated as a therapeutic strategy in metastatic uveal melanoma. This review will discuss preclinical and clinical studies evaluating selumetinib in metastatic uveal melanoma, as well as potential future perspectives on MEK inhibition in the management of metastatic uveal melanoma.
葡萄膜黑色素瘤是一种罕见但侵袭性强的黑色素瘤亚型。尽管进行了原发眼球摘除术或放射治疗，仍有近50%的患者会发生转移性疾病。目前对于转移性葡萄膜黑色素瘤尚无标准的护理治疗方法，也没有已被证明能延长总生存期的治疗方法。葡萄膜黑色素瘤的特征是通过G-α蛋白GNAQ和GNA11的突变激活包括MAPK途径和PI3K/AKT途径等在内的信号通路。用司美替尼抑制MEK已作为转移性葡萄膜黑色素瘤的一种治疗策略进行了评估。本综述将讨论评估司美替尼治疗转移性葡萄膜黑色素瘤的临床前和临床研究，以及MEK抑制在转移性葡萄膜黑色素瘤治疗中的潜在未来前景。
