(Chemical Equation Presented) Aurora serine/threonine-protein kinases localize in the centrosome and play a crucial role in cell division by regulating chromatid segregation in mitotic cells; moreover, defective chromatid segregation causes genetic instability, leading to tumorigenesis. Aurora kinases were first identified in Xenopus Eg2, yeast Ipl1 and Drosophila aurora. The human genome expresses three members of the mitotic Aurora kinase family: Aurora kinase A, B and C. Although Aurora kinase A and B are highly homologous, their localization and function differ during mitosis. Aurora kinase A and B have been extensively studied due to their overexpression in tumor cells. Since high AURKA gene expression has been correlated with centrosome amplification and Aurora kinase A is required for cytokinesis, defective Aurora kinase A may cause aneuploidy characteristic of tumors. Thus, inhibition of Aurora kinase A may prove to be therapeutically beneficial, and several inhibitors of Aurora kinase A are being tested in early-phase clinical trials. MLN-8237, a selective inhibitor of Aurora kinase A, is currently in phase I/II clinical trials in both adult and childhood solid tumors and hematological malignancies. Here we review the biology of Aurora kinase A and the role of MLN-8237 as a novel therapeutic agent for cancer.
ASJC Scopus subject areas
- Pharmacology (medical)