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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:
Figure 2B shows GNAQ and GNA11 mutant cell growth to be more sensitive to MEKi treatment than wild-type cells, reaching 50% of half-maximal growth inhibition at ∼1 log less nanomolar concentration....Mutant GNAQ [Q209L (92.1, MEL202), Q209P (MEL270)], mutant GNA11 [Q209L (OMM1, UPMD1, UPMD2)] or wild-type (MEL285, MEL290) uveal melanoma cells were treated with MEKi alone, PI3Ki alone, or the combination of MEKi + PI3Ki for 48 hrs...However, the combination of MEK + PI3K inhibition results in a strong induction of apoptotic death, most pronounced in GNAQ mutant cells, but also evident in the majority of GNA11 mutant cells.
DOI:
10.1158/1078-0432.CCR-11-3227