title: Aurora kinases as druggable targets in pediatric leukemia: heterogeneity in target modulation activities and cytotoxicity by diverse novel therapeutic agents.
abstract: Leukemia is the most common pediatric malignancy, constituting more than 30% of all childhood cancers. Although cure rates have improved greatly, approximately one in five children relapse and poor survival rates post relapse remain a challenge. Given this, more effective and innovative therapeutic strategies are needed in order to improve prognosis. Aurora kinases, a family of serine/threonine kinases essential for the regulation of several mitotic processes, have been identified as potential targets for cancer therapeutics. Elevated expression of Aurora kinases has been demonstrated in several malignancies and is associated with aberrant mitotic activity, aneuploidy and alterations in chromosomal structure and genome instability. Based on this rationale, a number of small molecule inhibitors have been formulated and advanced to human studies in the recent past. A comparative analysis of these agents in cytotoxicity and target modulation analyses against a panel of leukemia cells provides novel insights into the unique mechanisms and codependent activity pathways involved in targeting Aurora kinases, constituting a distinctive preclinical experimental framework to identify appropriate agents and combinations in future clinical studies.
authors.affiliation: Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Aarthi
authors.initials: A
authors.lastname: Jayanthan
authors.affiliation: Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada.
authors.forename: Yibing
authors.initials: Y
authors.lastname: Ruan
authors.affiliation: Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: Tony H
authors.initials: TH
authors.lastname: Truong
authors.affiliation: Pediatric Oncology Experimental Therapeutics Investigators Consortium (POETIC) Laboratory for Pre-Clinical and Drug Discovery Studies, University of Calgary, Calgary, Alberta, Canada; Division of Pediatric Oncology, Alberta Children's Hospital, Calgary, Alberta, Canada.
authors.forename: Aru
authors.initials: A
authors.lastname: Narendran
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D064127:Aurora Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002648:Child; D015316:Genetic Therapy; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D058990:Molecular Targeted Therapy; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000627:therapeutic use
chemical_list: D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D064127:Aurora Kinases