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Article

Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.

Cancer research - 17 Feb 2025

Ford Catriona A, Koludrovic Dana, Centeno Patricia P, Foth Mona, Tsonou Elpida, Vlahov Nikola, Sphyris Nathalie, Gilroy Kathryn, Bull Courtney, Nixon Colin, Serrels Bryan, Munro Alison F, Dawson John C, Carragher Neil O, Pavet Valeria, Hornigold David C, Dunne Philip D, Downward Julian, Welch Heidi C E, Barry Simon T, Sansom Owen J, Campbell Andrew D

Abstract excerpt

Metastatic melanoma remains a major clinical challenge. Large-scale genomic sequencing of melanoma has identified bona fide activating mutations in RAC1, which are associated with resistance to BRAF-targeting therapies. Targeting the RAC1-GTPase pathway, including the upstream activator PREX2 and the downstream effector PI3Kβ, could be a potential strategy for overcoming therapeutic resistance, limiting melanoma...

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Methodology Data sources Editorial policy Privacy Delete account & data About Contact Helena Bioinformatics

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Share to Proto-Oncogene Proteins B-raf

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Source

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Identifiers

PMID: 39636745
DOI: 10.1158/0008-5472.CAN-23-2814
PMCID: PMC11831108

Genes

PREX2
RAC1
BRAF

Provenance

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Related research

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Research trail→

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Targeting the PREX2/RAC1/PI3Kβ Signaling Axis Confers Sensitivity to Clinically Relevant Therapeutic Approaches in Melanoma.PMID 39636745Read ↗

A targetable PREX2/RAC1/PI3Kβ signalling axis confers resistance to clinically relevant therapeutic approaches in melanomaSemantic proximity Read ↗

ERK/MAPK Signaling Drives Overexpression of the Rac-GEF, PREX1, in BRAF- and NRAS-Mutant Melanoma.Semantic proximity Read ↗

Tumorigenesis driven by the BRAF <sup>V600E</sup> oncoprotein requires secondary mutations that overcome its feedback inhibition of migration and invasionSemantic proximity Read ↗

Truncating PREX2 mutations activate its GEF activity and alter gene expression regulation in NRAS-mutant melanoma.Semantic proximity Read ↗

Melanoma genome sequencing reveals frequent PREX2 mutations.Semantic proximity Read ↗

Tumorigenesis Driven by BRAFV600E Requires Secondary Mutations That Overcome Its Feedback Inhibition of RAC1 and Migration.Semantic proximity Read ↗

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