title: Hydralazine-valproate: a repositioned drug combination for the epigenetic therapy of cancer.
abstract: BACKGROUND
  DNA methylation (DNMTi) and histone deacetylase inhibitors (HDACi) are in development for cancer therapy. So far, four epigenetic drugs are approved for myelodysplastic syndrome (MDS) and cutaneous T-cell lymphoma (CTCL). The combination of hydralazine-valproate (TRANSKRIP(™)) is being repositioned as an oral DNMT and HDAC inhibitor.
  
  
  METHODS
  Brief discussion on the current status of epigenetic drugs and studies published on the preclinical and clinical development of the hydralazine-valproate combination.
  
  
  CONCLUSIONS
  Drug repositioning is a strategy for prompt and cost-efficient drug discovery. There is evidence that combining DNMTi with HDACi would be more efficacious than administering each agent on its own. Hydralazine-valproate is safe when used alone or in combination with chemotherapy or chemoradiation. The fact that both drugs are orally administered is another advantage over current epigenetic drugs. This combination is promising but larger studies are needed. Among these, the randomized Phase III trials in advanced and in locally advanced cervical cancer combined with chemotherapy and cisplatin-radiation respectively, would eventually confirm its efficacy. Studies on MDS and CTCL would also eventually prove the efficacy of hydralazine valproate so that in the coming years hydralazine-valproate could have a role in cancer epigenetic therapy.
authors.affiliation: Instituto de Investigaciones Biomédicas UNAM/Instituto Nacional de Cancerología Mexico, Unit of Biomedical Research on Cancer , Mexico City , Mexico.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Dueñas-Gonzalez
authors.forename: Jaime
authors.initials: J
authors.lastname: Coronel
authors.forename: Lucely
authors.initials: L
authors.lastname: Cetina
authors.forename: Aurora
authors.initials: A
authors.lastname: González-Fierro
authors.forename: Alma
authors.initials: A
authors.lastname: Chavez-Blanco
authors.forename: Lucia
authors.initials: L
authors.lastname: Taja-Chayeb
mesh_terms: D000284:Administration, Oral; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003131:Combined Modality Therapy; D019175:DNA Methylation / Q000187:drug effects; D058492:Drug Repositioning; D044127:Epigenesis, Genetic; D056572:Histone Deacetylase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D014635:Valproic Acid / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D056572:Histone Deacetylase Inhibitors; D006830:Hydralazine; D014635:Valproic Acid
keywords: cervical cancer; cutaneous T-cell lymphoma; drug repositioning; epigenetics; hydralazine; myelodysplastic syndrome; orphan drug; valproate