Synthetic Lethal Screens Reveal Cotargeting FAK and MEK as a Multimodal Precision Therapy for <i>GNAQ</i>-Driven Uveal Melanoma.

ABSTRACT:

Purpose

Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq-oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK-ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However,

SUBMITTER: Paradis JS 

PROVIDER: S-EPMC8895627 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature