Histone deacetylase inhibitors: a promising partner for MEK inhibitors in uveal melanoma?

摘要

Uveal melanoma is a highly aggressive tumor derived from the melanocytes of the eye. More than 90% of uveal melanomas harbor activating mutations in the small G-proteins GNAQ/GNA11 and have constitutive activity in the MAPK pathway [ ]. In uveal melanoma, GNAQ/GNA11 activates phospholipase C β, which cleaves phosphatidylinositol-4,5-biphosphate to diacyl glycerol and inositol triphosphate. Both of these products activate protein kinase C, which in turn activates the MAPK pathway. Constitutive signaling in other signal transduction cascades including the PI3K/AKT/mTOR, WNT/β-catenin and the YAP-signaling pathways have also been reported.