biostudies-literatureAraiza-Olivera DNCI NIH HHS944-952https://www.ebi.ac.uk/biostudies/studies/S-EPMC5814328biostudies-literatureUnknown37(7)Activating mutations in the RAC1 gene have recently been discovered as driver events in malignant melanoma. Expression of this gene is associated with melanocyte proliferation, and melanoma cells bearing this mutation are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune surveillance due to enhanced expression of PD-L1. Activating mutations in RAC1 are of special interest, as small-molecule inhibitors for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might impede oncogenic signaling from mutant RAC1. In this work, we explore the effects of PAK inhibition on RAC1^P29S signaling in zebrafish embryonic development, in the proliferation, survival and motility of RAC1^P29S-mutant human melanoOncogeneSuppression of RAC1-driven malignant melanoma by group A PAK inhibitors.PMC5814328R01 CA142928P30 CA006927Semenova GRhodes JFeng YAraiza-Olivera DPrudnikova TYChernoff JfalseSuppression of RAC1-driven malignant melanoma by group A PAK inhibitors.Activating mutations in the RAC1 gene have recently been discovered as driver events in malignant melanoma. Expression of this gene is associated with melanocyte proliferation, and melanoma cells bearing this mutation are insensitive to BRAF inhibitors such as vemurafenib and dabrafenib, and also may evade immune surveillance due to enhanced expression of PD-L1. Activating mutations in RAC1 are of special interest, as small-molecule inhibitors for the RAC effector p21-activated kinase (PAK) are in late-stage clinical development and might impede oncogenic signaling from mutant RAC1. In this work, we explore the effects of PAK inhibition on RAC1^P29S signaling in zebrafish embryonic development, in the proliferation, survival and motility of RAC1^P29S-mutant human melano2018-01-01T00:00:00Z2018 Feb2025-04-05T12:16:34.81Z2019-03-26T23:31:08ZS-EPMC58143282905917110.1038/onc.2017.400