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Erschienen in: Journal of Cancer Research and Clinical Oncology 9/2016

01.03.2016 | Review – Clinical Oncology

The Aurora kinase inhibitors in cancer research and therapy

verfasst von: Jonas Cicenas

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2016

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Abstract

Compounds that affect enzymatic function of kinases are valuable for the understanding of the complex biochemical processes in cells. Aurora kinases (AURKs) play a key role in the control of the mitosis. These kinases are frequently deregulated in different human cancers: overexpression, amplifications, translocations and deletions were reported in many cancer cell lines as well as patient tissues. These findings steered a rigorous hunt for small-molecule AURK inhibitors not only for research purposes as well as for therapeutic uses. In this review, we describe a number of AURK inhibitors and their use in cancer research and/or therapy. We hope to assist researchers and clinicians in deciding which inhibitor is most appropriate for their specific purpose. The review will also provide a broad overview of the clinical studies performed with some of these inhibitors (if such studies have been performed).
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Zurück zum Zitat Fu S, Li Y, Huang J, Liu T, Hong Z, Chen A, Bast RC, Kavanagh JJ, Gershenson DM, Sood AK, Hu W (2012) Aurora kinase inhibitor VE 465 synergistically enhances cytotoxicity of carboplatin in ovarian cancer cells through induction of apoptosis and downregulation of histone 3. Cancer Biol Ther 13(11):1034–1041. doi:10.4161/cbt.21045 PubMedPubMedCentralCrossRef Fu S, Li Y, Huang J, Liu T, Hong Z, Chen A, Bast RC, Kavanagh JJ, Gershenson DM, Sood AK, Hu W (2012) Aurora kinase inhibitor VE 465 synergistically enhances cytotoxicity of carboplatin in ovarian cancer cells through induction of apoptosis and downregulation of histone 3. Cancer Biol Ther 13(11):1034–1041. doi:10.​4161/​cbt.​21045 PubMedPubMedCentralCrossRef
Zurück zum Zitat Gabillard JC, Ulisse S, Baldini E, Sorrenti S, Cremet JY, Coccaro C, Prigent C, D’Armiento M, Arlot-Bonnemains Y (2011) Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. Biochem Biophys Res Commun 408(4):647–653. doi:10.1016/j.bbrc.2011.04.078 PubMedCrossRef Gabillard JC, Ulisse S, Baldini E, Sorrenti S, Cremet JY, Coccaro C, Prigent C, D’Armiento M, Arlot-Bonnemains Y (2011) Aurora-C interacts with and phosphorylates the transforming acidic coiled-coil 1 protein. Biochem Biophys Res Commun 408(4):647–653. doi:10.​1016/​j.​bbrc.​2011.​04.​078 PubMedCrossRef
Zurück zum Zitat Georgieva I, Koychev D, Wang Y, Holstein J, Hopfenmüller W, Zeitz M, Grabowski P (2010) ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines. Neuroendocrinology 91(2):121–130. doi:10.1159/000258705 PubMedCrossRef Georgieva I, Koychev D, Wang Y, Holstein J, Hopfenmüller W, Zeitz M, Grabowski P (2010) ZM447439, a novel promising aurora kinase inhibitor, provokes antiproliferative and proapoptotic effects alone and in combination with bio- and chemotherapeutic agents in gastroenteropancreatic neuroendocrine tumor cell lines. Neuroendocrinology 91(2):121–130. doi:10.​1159/​000258705 PubMedCrossRef
Zurück zum Zitat Geuns-Meyer S, Cee VJ, Deak HL, Du B, Hodous BL, Nguyen HN, Olivieri PR, Schenkel LB, Vaida KR, Andrews P, Bak A, Be X, Beltran PJ, Bush TL, Chaves MK, Chung G, Dai Y, Eden P, Hanestad K, Huang L, Lin MH, Tang J, Ziegler B, Radinsky R, Kendall R, Patel VF, Payton M (2015) Discovery of N-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine (AMG 900), a highly selective, orally bioavailable inhibitor of aurora kinases with activity against multidrug-resistant cancer cell lines. J Med Chem 58(13):5189–5207. doi:10.1021/acs.jmedchem.5b00183 PubMedCrossRef Geuns-Meyer S, Cee VJ, Deak HL, Du B, Hodous BL, Nguyen HN, Olivieri PR, Schenkel LB, Vaida KR, Andrews P, Bak A, Be X, Beltran PJ, Bush TL, Chaves MK, Chung G, Dai Y, Eden P, Hanestad K, Huang L, Lin MH, Tang J, Ziegler B, Radinsky R, Kendall R, Patel VF, Payton M (2015) Discovery of N-(4-(3-(2-aminopyrimidin-4-yl)pyridin-2-yloxy)phenyl)-4-(4-methylthiophen-2-yl)phthalazin-1-amine (AMG 900), a highly selective, orally bioavailable inhibitor of aurora kinases with activity against multidrug-resistant cancer cell lines. J Med Chem 58(13):5189–5207. doi:10.​1021/​acs.​jmedchem.​5b00183 PubMedCrossRef
Zurück zum Zitat Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ (2007) MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 109(2):500–502PubMedCrossRef Giles FJ, Cortes J, Jones D, Bergstrom D, Kantarjian H, Freedman SJ (2007) MK-0457, a novel kinase inhibitor, is active in patients with chronic myeloid leukemia or acute lymphocytic leukemia with the T315I BCR-ABL mutation. Blood 109(2):500–502PubMedCrossRef
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Zurück zum Zitat Goto H, Yasui Y, Kawajiri A, Nigg EA, Terada Y, Tatsuka M, Nagata K, Inagaki M (2003) Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J Biol Chem 278(10):8526–8530PubMedCrossRef Goto H, Yasui Y, Kawajiri A, Nigg EA, Terada Y, Tatsuka M, Nagata K, Inagaki M (2003) Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J Biol Chem 278(10):8526–8530PubMedCrossRef
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Zurück zum Zitat Hirota T, Kunitoku N, Sasayama T, Marumoto T, Zhang D, Nitta M, Hatakeyama K, Saya H (2003) Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 114(5):585–598PubMedCrossRef Hirota T, Kunitoku N, Sasayama T, Marumoto T, Zhang D, Nitta M, Hatakeyama K, Saya H (2003) Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 114(5):585–598PubMedCrossRef
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Zurück zum Zitat Kantarjian HM, Sekeres MA, Ribrag V, Rousselot P, Garcia-Manero G, Jabbour EJ, Owen K, Stockman PK, Oliver SD (2013) Phase I study assessing the safety and tolerability of barasertib (AZD1152) with low-dose cytosine arabinoside in elderly patients with AML. Clin Lymphoma Myeloma Leuk 13(5):559–567. doi:10.1016/j.clml.2013.03.019 PubMedPubMedCentralCrossRef Kantarjian HM, Sekeres MA, Ribrag V, Rousselot P, Garcia-Manero G, Jabbour EJ, Owen K, Stockman PK, Oliver SD (2013) Phase I study assessing the safety and tolerability of barasertib (AZD1152) with low-dose cytosine arabinoside in elderly patients with AML. Clin Lymphoma Myeloma Leuk 13(5):559–567. doi:10.​1016/​j.​clml.​2013.​03.​019 PubMedPubMedCentralCrossRef
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Metadaten
Titel
The Aurora kinase inhibitors in cancer research and therapy
verfasst von
Jonas Cicenas
Publikationsdatum
01.03.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2016
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-016-2136-1

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