Histone deacetylases (HDACs) as mediators of resistance to apoptosis in melanoma and as targets for combination therapy with selective BRAF inhibitors

Abstract

HDACs are viewed as enzymes used by cancer cells to inhibit tumor suppressor mechanisms. In particular, we discuss their role as suppressors of apoptosis in melanoma cells and as mediators of resistance to selective BRAF inhibitors. Synergistic increases in apoptosis are seen when pan-HDAC inhibitors are combined with selective BRAF inhibitors. Moreover, cell lines from patients with acquired resistance to Vemurafenib undergo PLX4720 induced apoptosis when combined with pan-HDAC inhibitors. The mechanisms of upregulation of HDACs and the mechanisms involved in HDACi reversal of resistance to apoptosis are as yet poorly understood.