A Genome-Wide Screen Identifies PDPK1 as a Target to Enhance the Efficacy of MEK1/2 Inhibitors in NRAS Mutant Melanoma

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

Automated summary

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.