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PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.

ABSTRACT: 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.

SUBMITTER: Davis TB

PROVIDER: S-EPMC6887575 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.

Davis Thomas B TB Yang Mingli M Wang Heiman H Lee Changgong C Yeatman Timothy J TJ Pledger W Jack WJ

Oncotarget 20191126 63

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 ...[more]

PMID: 31827720

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