期刊
CANCER RESEARCH
卷 82, 期 14, 页码 2625-2639出版社
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/0008-5472.CAN-21-3217
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资金
- NIH [R01 CA160495, R01 CA256945, P01 CA114046]
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation [P30 CA056036]
- NCI
In this study, it was demonstrated that loss of phosphoinositide-dependent kinase-1 (PDPK1) enhances the efficacy of MEKi, and the synergistic effects of PDPK1 loss and MEKi were validated in NRAS mutant melanoma cell lines.
ever, limited advance has been made in developing targeted therapy (MEKi) show modest efficacy in the clinic and their actions need to be optimized. In this study, we performed a genome-wide CRISPRCas9-based screen and demonstrated that loss of phosphoinositidedependent kinase-1 (PDPK1) enhances the efficacy of MEKi. The synergistic effects of PDPK1 loss and MEKi was validated in NRAS mutant melanoma cell lines using pharmacologic and molecular suppressed NRAS mutant xenograft growth and induced gasdermin
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