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Clinical Experience with Aurora Kinase Inhibitors: A Review

^aDivision of Clinical Pharmacology, Department of Medical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands; ^bUtrecht University, Faculty of Science, Department of Pharmaceutical Sciences, Section of Biomedical Analysis, Division of Drug Toxicology, Utrecht, The Netherlands; ^cDepartment of Pharmacy and Pharmacology, Slotervaart Hospital, Amsterdam, The Netherlands

Key Words. Aurora kinase • Mitosis • Targeted therapy • Drug development • Clinical trial

Correspondence: Correspondence: Jan H.M. Schellens, M.D., Ph.D., The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Telephone: 31-20-512-2569; Fax: 31-20-512-2572; e-mail: jhm{at}nki.nl

Received February 1, 2009; accepted for publication July 6, 2009.

Disclosures: David S. Boss: None; Jos H. Beijnen: None; Jan H.M. Schellens: Consultant/advisory role: AstraZeneca; Research funding/contracted research: AstraZeneca.

The aurora kinase family of serine/threonine kinases comprises three members, designated auroras A, B, and C. Auroras A and B are essential components of the mitotic pathway, ensuring proper chromosome assembly, formation of the mitotic spindle, and cytokinesis. The role of aurora C is less clear. Overexpression of aurora A and B has been observed in several tumor types, and has been linked with a poor prognosis of cancer patients. Several small molecules targeting aurora kinases A and B or both have been evaluated preclinically and in early phase I trials. In this review we aim to summarize the most recent advances in the development of aurora kinase inhibitors, with a focus on the clinical data.