2015 Antineoplastics



  • HDAC mechanismhistone deacetylases (HDACs) work in conjunction with histone acetyltransferases to regulate gene expression
    • acetylation is associated with euchromatin ("open for transcription")
    • deacetylation is associated with heterochromatin ("closed")

  • some cancer cells overexpress or aberrently recruit HDACs, leading to hypoacetylation of histones, condensed chromatin structure and decreased transcription
    • causes silencing of tumor suppressor genes (esp. p53)

  • HDAC inhibitors increase transcription, and lead to cell cycle arrest and apoptosis

  • valproic acid (a 1st generation HDAC inhibitor that is approved for use as a mood stabilizer and as an antiepileptic) is under investigation for use in cancer
    • HDAC inhibitors are also under active investigation for use in Huntington's disease and ALS

  • VORINOSTAT is approved for use in cutaneous T-cell lymphoma, and is under investigation in glioblastoma multiforme and HIV

  • VORINOSTAT undergoes hepatic metabolism (but not by CYP450), and it is not a substrate for P-glycoprotein
Email: Dr. Janet Fitzakerley | ©2015 University of Minnesota Medical School Duluth | Last modified: 10-may-15 8:08 PM