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.
|Original language||English (US)|
|Title of host publication||Molecular Oncology|
|Subtitle of host publication||Causes of Cancer and Targets for Treatment|
|Publisher||Cambridge University Press|
|Number of pages||15|
|State||Published - Jan 1 2015|
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