title: Targeting VDAC-bound hexokinase II: a promising approach for concomitant anti-cancer therapy.
abstract: BACKGROUND
  Enhancement of glucose metabolism and repression of oxidative phosphorylation followed by the Warburg effect is the common hallmark of cancer cells. Hexokinase II (HKII) plays a dual role - first, HKII up-regulation results in increased glycolysis rates. Second, association of VDAC and HKII contributes to inhibition of apoptosis through repression of the formation of mitochondrial permeability transition pores.
  
  
  METHODS
  In this review, the role of HKII in evasion of apoptosis, aspects of HKII expression regulation, novel approaches targeting HKII and VDAC-HKII complexes and their application areas are discussed.
  
  
  CONCLUSIONS
  The dual role of HKII in cancer cells makes it an attractive target for anti-cancer therapy. Several agents, either synthetic or plant-derived, that target hexokinase and induce VDAC-HK complex dissociation have been identified to date. Targeting hexokinase, HK-VDAC complexes as well as other glycolytic proteins not only improves the efficacy of commonly used drugs. The most prominent benefit of this approach is the ability to overcome drug resistance, for example, to cisplatin or sorafenib. In some cases, it could create an insurmountable challenge for selection of appropriate therapy. Future studies and trials should address the issue of how to transfer these approaches into clinical practice.
authors.affiliation: Engelhardt Institute of Molecular Biology RAS , Moscow , Russia rhizamoeba@mail.ru.
authors.forename: George S
authors.initials: GS
authors.lastname: Krasnov
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Dmitriev
authors.forename: Valentina A
authors.initials: VA
authors.lastname: Lakunina
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Kirpiy
authors.forename: Anna V
authors.initials: AV
authors.lastname: Kudryavtseva
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology; D006593:Hexokinase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D050994:Voltage-Dependent Anion Channels / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D050994:Voltage-Dependent Anion Channels; D006593:Hexokinase