title: 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.
authors.affiliation: Oncology and Immunology Unit, University of Newcastle, Newcastle, Australia.
authors.forename: Fritz
authors.initials: F
authors.lastname: Lai
authors.forename: Lei
authors.initials: L
authors.lastname: Jin
authors.forename: Stuart
authors.initials: S
authors.lastname: Gallagher
authors.forename: Branka
authors.initials: B
authors.lastname: Mijatov
authors.forename: Xu Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Peter
authors.initials: P
authors.lastname: Hersey
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D048493:Proto-Oncogene Proteins B-raf; D006655:Histone Deacetylases