PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.
PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.
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DOI：
10.18632/oncotarget.27335
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发表时间：
2019-11-26
期刊：
影响因子：
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通讯作者：
Pledger, W Jack
中科院分区：
文献类型：
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作者：
Davis, Thomas B;Yang, Mingli;Pledger, W Jack
PTPRS是结直肠癌（CRC）中最常见的突变受体酪氨酸磷酸酶。PTPRS已被证明直接影响ERK并调节其活化和核定位。在这里，我们确定PTPRS可能通过SRC激活在发展对MEK/ERK抑制剂（MEKi/ERKi）的适应性抗性中发挥重要作用。此外，我们证明了一种新的临床方法，通过使用SRC抑制剂达沙替尼来避免适应性耐药。我们的数据表明，达沙替尼有可能通过阻止SRC的适应性耐药途径来增强MEKi和ERKi的疗效。
PTPRS is the most commonly mutated receptor tyrosine phosphatase in colorectal cancer (CRC). PTPRS has been shown to directly affect ERK and regulate its activation and nuclear localization. Here we identify that PTPRS may play a significant role in developing adaptive resistance to MEK/ERK inhibitors (MEKi/ERKi) through SRC activation. Moreover, we demonstrate a new clinical approach to averting adaptive resistance through the use of the SRC inhibitor, dasatinib. Our data suggest the potential for dasatinib to enhance the efficacy of MEKi and ERKi by preventing adaptive resistance pathways operating through SRC.