Mutant BRAF Melanomas-Dependence and Resistance

被引：218

作者：

Poulikakos, Poulikos I. ^{[1
,2
]}

Rosen, Neal ^{[1
,2
]}

机构：

[1] Mem Sloan Kettering Canc Ctr, Program Mol Pharmacol & Chem, New York, NY 10065 USA

[2] Mem Sloan Kettering Canc Ctr, Dept Med, New York, NY 10065 USA

来源：

CANCER CELL | 2011年 / 19卷 / 01期

关键词：

ACQUIRED-RESISTANCE; MEK INHIBITORS; RAF; PATHWAY; CELLS; AKT; AMPLIFICATION; ACTIVATION; CANCER; GENE;

D O I：

10.1016/j.ccr.2011.01.008

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 [肿瘤学];

摘要：

RAF inhibitors have the unique property of transactivating RAS-dependent RAF dimers in most cells but inhibit RAF/MEK/ERK signaling in cells expressing mutant BRAF, in which RAS activity is too low to support this process. These drugs thus selectively inhibit ERK signaling in tumors with BRAF mutation. RAF inhibitors have remarkable clinical activity in melanomas with BRAFV600E mutations; however, resistance invariably develops. Three recent papers reveal that acquired resistance may be due to mechanisms that cause ERK signaling to become insensitive to RAF inhibitors, or that reduce the dependence of the tumor on ERK signaling through activation of other pathways.

引用

页码：11 / 15

页数：5

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