Aurora kinase inhibitors: identification and preclinical validation of their biomarkers.
Aurora kinases are key regulators of mitosis and inhibitors being developed by a wide range of pharmaceutical and biotechnology companies for the treatment of cancer. Tumor cells respond differentially on inhibition of different Aurora kinase family members and these differences have to be considered in the clinical development of small-molecule inhibitors with respect to the chosen indications, the schedules or the selection of appropriate end points and they should also guide the development of biomarkers. Preclinical validation of potential biomarkers for Aurora kinase inhibitors led to a first application in clinical trials, as exemplified for the phosphorylation of histone H3 to follow Aurora-B inhibition. This review discusses the criteria for translation into the clinic and the value of pharmacodynamic biomarkers and their potential, but also their limitations to be used as surrogate markers for clinical end points.
Carpinelli
Patrizia
P
Nerviano Medical Sciences Srl. Viale Pasteur 10, 20014 Nerviano (Mi), Italy.
Moll
Jürgen
J
D000818:Animals; D064107:Aurora Kinase B; D064127:Aurora Kinases; D015415:Biomarkers / Q000378:metabolism; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000378:metabolism / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015203:Reproducibility of Results
D015415:Biomarkers; D047428:Protein Kinase Inhibitors; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases