Aurora kinase inhibitors in preclinical and clinical testing

Abstract

Background: Mitosis is a key step in the cell cycle governing the distribution of genetic material to the daughter cells. Any aberration in this process could lead to genomic instability. Aurora A, B and C, are members of the serine/threonine kinase family. Aurora kinases are essential for spindle assembly, centrosome maturation, chromosomal segregation and cytokinesis during mitosis. Abnormalities in the mitotic process through overexpression/amplification of aurora kinase have been linked to genomic instability leading to tumorigenesis. Hence, use of aurora kinase small molecule inhibitors as potential molecular-targeted therapeutic intervention for cancer is being pursued by various researchers. Objective: To review the literature of aurora kinase inhibitors in clinical and preclinical testing. Method: Pubmed, Scifinder® and www.clinicaltrials.gov databases were used to search the literature for aurora kinase. Conclusion/results: Approximately 13 aurora kinase inhibitors are under Phase I/II evaluation at present for various cancers of different origins; and several others are in preclinical testing. Details of their preclinical/clinical results and important considerations for future aurora kinase inhibitor development are discussed. Considering the fact that aurora kinase plays an important role in the mitosis process and is involved in tumorigenesis, development of aurora kinase inhibitors for the treatment of cancer, either as a single agent or in combination with existing cancer treatment is warranted.