Inhibition of the RAC/PAK Signaling Axis Enhances the Potency of MAPK Cascade Inhibitors Against Uveal Melanoma.

ABSTRACT: Uveal melanoma is a melanocyte-derived malignancy of the eye with a high propensity for liver metastasis. Metastatic uveal melanoma is associated with high mortality and is poorly responsive to currently available therapies. Most uveal melanoma cases are driven by activating mutations in GNAQ and GNA11 genes, which convey oncogenic signaling through the mitogen-activated protein kinase (MAPK) pathway. Despite promising early results, safe doses of pharmacological inhibitors of the MAPK cascade failed to effectively control uveal melanoma in human trials. Considering the role of the RAC/PAK signaling axis as a co-regulator of the MAPK cascade, we set forth to investigate whether the efficacy of MAPK cascade inhibitors in pre-clinical models may be enhanced by direct inhibition of RAC and PA

SUBMITTER: Maslov AA 

PROVIDER: S-EPMC12564536 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature