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Accession IconGSE39984

Comparison of the genetic extinction of NRAS to pharmacological MEK inhibition in an inducible mouse model of melanoma

Organism Icon Mus musculus
Sample Icon 15 Downloadable Samples
Technology Badge Icon Affymetrix Mouse Genome 430 2.0 Array (mouse4302)

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Since direct pharmacological inhibition of RAS has thus far been unsuccessful, we explored system biology approaches to identify synergistic drug combination(s) that can mimic direct RAS inhibition. Leveraging an inducible mouse model of NRAS-mutant melanoma, we compare pharmacological MEK inhibition to complete NRAS-Q61K extinction in vivo. NRAS-Q61K extinction leads to a complete and durable tumor regression by enhancing both apoptosis and cell cycle arrest. By contrast, MEK inhibition only produces tumor stasis at best and we find that it robustly activates apoptosis but does not significantly impede proliferation.
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