Neratinib and entinostat combine to rapidly reduce the expression of K-RAS, N-RAS, Gαq and Gα11 and kill uveal melanoma cells

Abstract excerpt

There is no efficacious standard of care therapy for uveal melanoma. Unlike cutaneous disease, uveal melanoma does not exhibit RAS mutations but instead contains mutations with ~90% penetrance in either Gαq or Gα11. Previously we demonstrated that neratinib caused ERBB1/2/4 and RAS internalization into autolysosomes which resulted in their proteolytic degradation. In PDX isolates of uveal melanoma, neratinib...

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