title: Targeting of polo-like kinases and their cross talk with Aurora kinases--possible therapeutic strategies in human acute myeloid leukemia?
abstract: BACKGROUND
  Five human polo-like kinases (PLKs) have been identified, and PLK1 - 4 seem to interact with Aurora kinases and act as cell cycle regulators in both normal and malignant human cells.
  
  
  METHODS
  The present review describes i) experimental evidence for a role for PLKs and Aurora kinases in human leukemogenesis and ii) the results from clinical studies of PLK and Aurora kinase inhibitors in the treatment of human acute myeloid leukemia (AML). The review was based on searches in the PubMed and the ClinicalTrials.gov databases. These inhibitors have antiproliferative and proapoptotic effects in AML cells. Hematological and gastrointestinal toxicities are frequently dose limiting, and this may limit the use of these agents in combination with conventional AML therapy. Aurora kinase inhibitors seem to be most effective for patients with high expression of the target kinases, and the same may be true for PLK inhibitors.
  
  
  CONCLUSIONS
  PLK inhibition is a promising strategy for the treatment of AML. Future clinical studies have to clarify i) whether this strategy is most effective for certain subsets of patients; ii) whether multikinase inhibitors targeting several cell cycle regulators should be preferred; and iii) how this therapeutic strategy eventually should be combined with conventional antileukemic chemotherapy.
authors.affiliation: Haukeland University Hospital, Division for Haematology, Department of Medicine, Bergen, Norway.
authors.forename: Galina
authors.initials: G
authors.lastname: Tsykunova
authors.forename: Håkon
authors.initials: H
authors.lastname: Reikvam
authors.forename: Aymen Bushra
authors.initials: AB
authors.lastname: Ahmed
authors.forename: Ina
authors.initials: I
authors.lastname: Nepstad
authors.forename: Bjørn Tore
authors.initials: BT
authors.lastname: Gjertsen
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D064127:Aurora Kinases; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases