title: Heat shock protein 70 - the next chaperone to target in the treatment of human acute myelogenous leukemia?
abstract: BACKGROUND
  Heat shock proteins (HSPs) are molecular chaperones that stabilize folding and conformation of mature proteins. HSPs are, therefore, considered as possible therapeutic targets in the treatment of human cancers, including acute myeloid leukemia (AML). This strategy offers the possibility of targeting several oncogenic proteins or several intracellular signaling pathways through the use of a single therapeutic agent.
  
  
  METHODS
  Several specific HSP70 inhibitors have now been developed. We describe: i) the molecular structure of HSP70 and the molecular interactions especially with its co-chaperones; ii) the immunoregulatory functions of HSP70; iii) the expression and function of HSP70 in human AML cells; iv) the molecular and pharmacological characteristics of potential HSP70 inhibitors; and v) the clinical and experimental studies of HSP70 inhibition in human AML. Our review is based on careful selection of relevant publications identified in the PubMed database.
  
  
  CONCLUSIONS
  HSP70 inhibitors have antileukemic activity in human AML. However, additional experimental studies using in vitro models as well as animal models are required, including detailed toxicology studies, as a scientific basis for the optimal design of future clinical studies.
authors: University of Bergen, Division for Hematology, Department of Clinical Science, Faculty of Medicine and Dentistry , Bergen , Norway.
authors: Håkon
authors: H
authors: Reikvam
authors: Annette K
authors: AK
authors: Brenner
authors: Ina
authors: I
authors: Nepstad
authors: André
authors: A
authors: Sulen
authors: Øystein
authors: Ø
authors: Bruserud
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D015195:Drug Design; D018840:HSP70 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D058990:Molecular Targeted Therapy; D011487:Protein Conformation; D017510:Protein Folding
chemical_list: D000970:Antineoplastic Agents; D018840:HSP70 Heat-Shock Proteins
keywords: acute myelogenous leukemia; heat shock protein 70; heat shock protein 70 inhibitors; immunoregulation