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23 - Aurora kinases in cancer: an opportunity for targeted therapy

from Part 2.1 - Molecular pathways underlying carcinogenesis: signal transduction

Published online by Cambridge University Press:  05 February 2015

By
Vikas Sehdev ,
Altaf A. Dar  and
Wael El-Rifai
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Vikas Sehdev
Affiliation:
Department of Surgery and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Altaf A. Dar
Affiliation:
California Paciic Medical Center Research Institute, San Francisco, CA, USA
Wael El-Rifai
Affiliation:
Department of Surgery and Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
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Summary

The Aurora kinase (AK) family members, Aurora kinase A (AURKA), Aurora kinase B (AURKB), and Aurora kinase C (AURKC) are a collection of highly related and conserved serine/threonine kinases that regulate key cellular functions, mitosis, and multiple signaling pathways. AK dysfunction can cause aneuploidy, mitotic arrest, and cell death. Several studies have reported amplification and/or over-expression of AURKA and AURKB in various human cancers. Additionally, transgenic mouse model studies have established AURKA as a bona fide oncogene. AURKA over-expression in tumors is often associated with gene amplification, genetic instability, dedifferentiated morphology, and poor prognosis. AURKB over-expression is frequently observed in a variety of tumors along with AURKA. AURKB over-expression has also been correlated with increased genetic instability and poor clinical outcome. The function of AURKC in cancer biology is relatively less studied. Given their association with tumorigenesis, both AURKA and AURKB have been targeted for cancer therapy. Currently, a number of selective and non-selective AK inhibitors are being tested in pre-clinical and clinical settings as anti-tumor agents. This chapter reviews the structure, biology and physiological functions of AKs and is an overview of small-molecule modulators of AKs for targeted cancer therapy.

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 278 - 292
Publisher: Cambridge University Press
Print publication year: 2013

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