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Association details:
Evidence:
Evidence Level:
Sensitive: D – Preclinical
New
Title:

Combination Small Molecule MEK and PI3K Inhibition Enhances Uveal Melanoma Cell Death in a Mutant GNAQ and GNA11 Dependent Manner

Excerpt:
Cells were cultured in RPMI 1640 supplemented with 5% fetal bovine serum at 37°C in a humidified 5% CO2 atmosphere. The MEK inhibitor, GSK1120212 (MEKi), and PI3K inhibitor, GSK2126458...GNAQ mutant, GNA11 mutant, or wild-type cells were treated with MEKi alone, PI3Ki alone, or the combination of MEKi + PI3Ki.GNAQ mutant cells demonstrated a marked induction of early apoptosis after MEKi + PI3Ki combination treatment (70% in MEL270, 55% in 92.1, and 44% in MEL202). GNA11 mutant and wild-type cells displayed a variable apoptotic response to MEKi + PI3Ki combination treatment (GNA11 = 20% in UPMD2, 20% in OMM1, 4% in UPMD1; wild-type = 5% in MEL285 and 7% in MEL290).
DOI:
10.1158/1078-0432.CCR-11-3227