Combined Inhibition of Gα_q and MEK Enhances Therapeutic Efficacy in Uveal Melanoma.

ABSTRACT:

Purpose

All uveal melanoma and a fraction of other melanoma subtypes are driven by activation of the G-protein alpha-q (Gα_q) pathway. Targeting these melanomas has proven difficult despite advances in the molecular understanding of key driver signaling pathways in the disease pathogenesis. Inhibitors of Gα_q have shown promising preclinical results, but their therapeutic activity in distinct Gα_q mutational contexts and in vivo have remained elusive.

Experimental design

We used an isogenic melanocytic cellular system to systematically examine hotspot mutations in GNAQ (e.g., G48V, R183Q, Q209L) and CYSLTR2 (L129Q) found in human uveal melanoma. This cellular system and human uveal melanoma cell lines were used in vitro</

SUBMITTER: Hitchman TD 

PROVIDER: S-EPMC8086191 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature