Targeting mutant NRAS signaling pathways in melanoma.
Targeting mutant NRAS signaling pathways in melanoma.
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DOI：
10.1016/j.phrs.2016.03.007
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发表时间：
2016-05
影响因子：
9.3
通讯作者：
Aplin AE
中科院分区：
文献类型：
--
作者：
Vu HL;Aplin AE
皮肤黑色素瘤是皮肤癌的一种毁灭性形式，其发病率在美国比任何其他可预防的癌症增长得更快。与非NRAS突变型黑色素瘤相比，黑色素瘤的突变型NRAS子集更具侵袭性，并且与较差的结局相关。这种转化所赋予的侵袭性和复杂的分子信号传导已经回避了临床有效的治疗选择。本文综述了黑色素瘤中NRAS相关的主要下游效应子，以及针对这些效应子通路的靶向治疗的相关进展。我们概述了突变型NRAS黑色素瘤中MEK抑制的历史以及新MEK抑制剂的最新进展。由于MEK抑制剂在与其他靶向治疗组合时可能会得到优化，因此我们专注于最近确定的可与MEK抑制剂组合使用的靶标。
Cutaneous melanoma is a devastating form of skin cancer and its incidence is increasing faster than any other preventable cancer in the United States. The mutant NRAS subset of melanoma is more aggressive and associated with poorer outcomes compared to non-NRAS mutant melanoma. The aggressive nature and complex molecular signaling conferred by this transformation has evaded clinically effective treatment options. This review examines the major downstream effectors of NRAS relevant in melanoma and the associated advances made in targeted therapies that focus on these effector pathways. We outline the history of MEK inhibition in mutant NRAS melanoma and recent advances with newer MEK inhibitors. Since MEK inhibitors will likely be optimized when combined with other targeted therapies, we focus on recently identified targets that can be used in combination with MEK inhibitors.