Aurora-A Kinase: A Potent Oncogene and Target for Cancer Therapy

Min Yan; Chunli Wang; Bin He; Mengying Yang; Mengying Tong; Zijie Long; Bing Liu; Fei Peng; Lingzhi Xu; Yan Zhang; Dapeng Liang; Haixin Lei; Sen Subrata; Keith W Kelley; Eric W-F Lam; Bilian Jin; Quentin Liu

doi:10.1002/med.21399

Aurora-A Kinase: A Potent Oncogene and Target for Cancer Therapy

Med Res Rev. 2016 Nov;36(6):1036-1079. doi: 10.1002/med.21399. Epub 2016 Jul 13.

Authors

Min Yan^{1

2}, Chunli Wang³, Bin He¹, Mengying Yang³, Mengying Tong³, Zijie Long⁴, Bing Liu³, Fei Peng³, Lingzhi Xu³, Yan Zhang¹, Dapeng Liang³, Haixin Lei³, Sen Subrata⁵, Keith W Kelley^{6

7}, Eric W-F Lam⁸, Bilian Jin⁹, Quentin Liu^{10

11

12}

Affiliations

¹ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
² Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
³ Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China.
⁴ Institute of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
⁵ Department of Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
⁶ Laboratory of Immunophysiology, Department of Animal Sciences, College of ACES, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁷ Department of Pathology, College of Medicine, University of Illinois at Urbana-Champaign, Urbana, IL, USA.
⁸ Department of Surgery and Cancer, Imperial College London, London, UK.
⁹ Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China. jinbilian@dmu.edu.cn.
¹⁰ State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China. liuq9@mail.sysu.edu.cn.
¹¹ Institute of Cancer Stem Cell, Cancer Center, Dalian Medical University, Dalian, China. liuq9@mail.sysu.edu.cn.
¹² Institute of Hematology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. liuq9@mail.sysu.edu.cn.

PMID: 27406026
DOI: 10.1002/med.21399

Abstract

The Aurora kinase family is comprised of three serine/threonine kinases, Aurora-A, Aurora-B, and Aurora-C. Among these, Aurora-A and Aurora-B play central roles in mitosis, whereas Aurora-C executes unique roles in meiosis. Overexpression or gene amplification of Aurora kinases has been reported in a broad range of human malignancies, pointing to their role as potent oncogenes in tumorigenesis. Aurora kinases therefore represent promising targets for anticancer therapeutics. A number of Aurora kinase inhibitors (AKIs) have been generated; some of which are currently undergoing clinical evaluation. Recent studies have unveiled novel unexpected functions of Aurora kinases during cancer development and the mechanisms underlying the anticancer actions of AKIs. In this review, we discuss the most recent advances in Aurora-A kinase research and targeted cancer therapy, focusing on the oncogenic roles and signaling pathways of Aurora-A kinases in promoting tumorigenesis, the recent preclinical and clinical AKI data, and potential alternative routes for Aurora-A kinase inhibition.

Keywords: Aurora kinase inhibitors (AKIs); Aurora-A; mitosis; targeted cancer therapy; tumorigenesis.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents / administration & dosage
Antineoplastic Agents / pharmacology*
Antineoplastic Combined Chemotherapy Protocols / pharmacology
Aurora Kinase A / antagonists & inhibitors*
Aurora Kinase A / genetics*
Aurora Kinase A / metabolism
Humans
Molecular Targeted Therapy
Neoplasms / drug therapy*
Neoplasms / enzymology
Neoplasms / genetics
Oncogenes
Protein Kinase Inhibitors / administration & dosage
Protein Kinase Inhibitors / pharmacology*

Substances

Antineoplastic Agents
Protein Kinase Inhibitors
Aurora Kinase A

Grants and funding

BBS/B/03785/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom