Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives
Selumetinib for the treatment of metastatic uveal melanoma: past and future perspectives
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DOI：
10.2217/fon-2015-0075
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发表时间：
2016-06-01
期刊：
影响因子：
3.3
通讯作者：
Carvajal, Richard D.
中科院分区：
文献类型：
--
作者：
Komatsubara, Kimberly M.;Manson, Daniel K.;Carvajal, Richard D.
葡萄膜黑色素瘤是一种罕见但具有侵袭性的黑色素瘤亚型。近50%的患者将发展为转移性疾病，尽管原发性眼球摘除术或放射治疗。目前没有转移性葡萄膜黑色素瘤的标准治疗，也没有已显示可延长总生存期的治疗。葡萄膜黑色素瘤的特征在于通过G-α蛋白GNAQ和GNA 11中的突变激活信号传导途径，包括MAPK途径和PI 3 K/AKT途径等。已将司美替尼抑制MEK作为转移性葡萄膜黑色素瘤的治疗策略进行了评价。本综述将讨论临床前和临床研究评估selumetinib在转移性葡萄膜黑色素瘤，以及潜在的未来前景MEK抑制在转移性葡萄膜黑色素瘤的管理。
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-alpha-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.