Combined MAPK Pathway and HDAC Inhibition Breaks Melanoma.

In this issue, Maertens and colleagues demonstrate that HDAC3 inhibition potentiates the effects of MAPK pathway inhibitors in melanoma, including difficult-to-treat NRAS- and NF1-driven tumors, with MGMT expression serving as a biomarker for responsiveness to the BRAF/MEK/HDAC inhibitor combination. Mechanistically, this triple cocktail suppresses expression of genes involved in DNA repair, leading to enhanced killing of melanoma cells.See related article by Maertens et al., p. 526.