Aurora kinase A inhibitors: promising agents in antitumoral therapy

Bibliography

• Perez de Castro I, de Carcer G, Malumbres M. A census of mitotic cancer genes: new insights into tumor cell biology and cancer therapy. Carcinogenesis 2007;28(5):899-912
   PubMed Web of Science ®Google Scholar
• Chan KS, Koh CG, Li HY. Mitosis-targeted anti-cancer therapies: where they stand. Cell Death Dis 2012;3:e411
   PubMed Web of Science ®Google Scholar
• Doménech E, Malumbres M. Mitosis-targeting therapies: a troubleshooting guide. Curr Opin Pharmacol 2013;13(4):519-28
   Google Scholar
• Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol 2003;4(11):842-54
   PubMed Web of Science ®Google Scholar
• Chan CS, Botstein D. Isolation and characterization of chromosome-gain and increase-in-ploidy mutants in yeast. Genetics 1993;135(3):677-91
   Google Scholar
• Cowley DO, Rivera-Pérez JA, Schliekelman M, et al. Aurora-A kinase is essential for bipolar spindle formation and early development. Mol Cell Biol 2009;29(4):1059-71
   PubMed Web of Science ®Google Scholar
• Lu LY, Wood JL, Ye L, et al. Aurora A is essential for early embryonic development and tumor suppression. J Biol Chem 2008;283(46):31785-90
   Google Scholar
• Sasai K, Parant JM, Brandt ME, et al. Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. Oncogene 2008;27(29):4122-7
   Google Scholar
• Fernández-Miranda G, Trakala M, Martín J, et al. Genetic disruption of aurora B uncovers an essential role for aurora C during early mammalian development. Development 2011;138(13):2661-72
   Google Scholar
• Dieterich K, Soto Rifo R, Faure AK, et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 2007;39(5):661-5
   Google Scholar
• Glover DM, Leibowitz MH, McLean DA, Parry H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 1995;81(1):95-105
   PubMed Web of Science ®Google Scholar
• Eyers PA, Erikson E, Chen LG, Maller JL. A novel mechanism for activation of the protein kinase Aurora A. Curr Biol 2003;13(8):691-7
   PubMed Web of Science ®Google Scholar
• Tsai MY, Wiese C, Cao K, et al. A Ran signalling pathway mediated by the mitotic kinase Aurora A in spindle assembly. Nat Cell Biol 2003;5(3):242-8
   Google Scholar
• Zhao ZS, Lim JP, Ng YW, et al. The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A. Mol Cell 2005;20(2):237-49
   Google Scholar
• Van Horn RD, Chu S, Fan L, et al. Cdk1 activity is required for mitotic activation of aurora A during G2/M transition of human cells. J Biol Chem 2010;285(28):21849-57
   Google Scholar
• Hirota T, Kunitoku N, Sasayama T, et al. Aurora-A and an interacting activator, the LIM protein Ajuba, are required for mitotic commitment in human cells. Cell 2003;114(5):585-98
   PubMed Web of Science ®Google Scholar
• Huang YH, Wu CC, Chou CK, Huang CY. A translational regulator, PUM2, promotes both protein stability and kinase activity of Aurora-A. PLoS One 2011;6(5):e19718
   Google Scholar
• Hutterer A, Berdnik D, Wirtz-Peitz F, et al. Mitotic activation of the kinase Aurora-A requires its binding partner Bora. Dev Cell 2006;11(2):147-57
   PubMed Web of Science ®Google Scholar
• Joukov V, De Nicolo A, Rodriguez A, et al. Centrosomal protein of 192 kDa (Cep192) promotes centrosome-driven spindle assembly by engaging in organelle-specific Aurora A activation. Proc Natl Acad Sci USA 2010;107(49):21022-7
   Google Scholar
• den Hollander J, Rimpi S, Doherty JR, et al. Aurora kinases A and B are up-regulated by Myc and are essential for maintenance of the malignant state. Blood 2010;116(9):1498-505
   PubMed Web of Science ®Google Scholar
• Reboutier D, Troadec MB, Cremet JY, et al. Nucleophosmin/B23 activates Aurora A at the centrosome through phosphorylation of serine 89. J Cell Biol 2012;197(1):19-26
   Google Scholar
• Pugacheva EN, Jablonski SA, Hartman TR, et al. HEF1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007;129(7):1351-63
   PubMed Web of Science ®Google Scholar
• Kufer TA, Silljé HH, Körner R, et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 2002;158(4):617-23
   PubMed Web of Science ®Google Scholar
• Bayliss R, Sardon T, Vernos I, Conti E. Structural basis of Aurora-A activation by TPX2 at the mitotic spindle. Mol Cell 2003;12(4):851-62
   PubMed Web of Science ®Google Scholar
• Zorba A, Buosi V, Kutter S, et al. Molecular mechanism of Aurora A kinase autophosphorylation and its allosteric activation by TPX2. Elife 2014;3:e02667
   PubMed Web of Science ®Google Scholar
• Littlepage LE, Ruderman JV. Identification of a new APC/C recognition domain, the A box, which is required for the Cdh1-dependent destruction of the kinase Aurora-A during mitotic exit. Genes Dev 2002;16(17):2274-85
   Google Scholar
• Shao S, Wang Y, Jin S, et al. Gadd45a interacts with aurora-A and inhibits its kinase activity. J Biol Chem 2006;281(39):28943-50
   Google Scholar
• Zeng K, Bastos RN, Barr FA, Gruneberg U. Protein phosphatase 6 regulates mitotic spindle formation by controlling the T-loop phosphorylation state of Aurora A bound to its activator TPX2. J Cell Biol 2010;191(7):1315-32
   Google Scholar
• Kiat LS, Hui KM, Gopalan G. Aurora-A kinase interacting protein (AIP), a novel negative regulator of human Aurora-A kinase. J Biol Chem 2002;277(47):45558-65
   Google Scholar
• Fumoto K, Lee PC, Saya H, Kikuchi A. AIP regulates stability of Aurora-A at early mitotic phase coordinately with GSK-3beta. Oncogene 2008;27(32):4478-87
   Google Scholar
• Kwon YW, Kim IJ, Wu D, et al. Pten regulates Aurora-A and cooperates with Fbxw7 in modulating radiation-induced tumor development. Mol Cancer Res 2012;10(6):834-44
   Google Scholar
• Shi Y, Solomon LR, Pereda-Lopez A, et al. Ubiquitin-specific cysteine protease 2a (USP2a) regulates the stability of Aurora-A. J Biol Chem 2011;286(45):38960-8
   Google Scholar
• Chen SS, Chang PC, Cheng YW, et al. Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function. EMBO J 2002;21(17):4491-9
   PubMedGoogle Scholar
• Perez de Castro I, Aguirre-Portoles C, Martin B, et al. A SUMOylation motif in Aurora-A: implications for spindle dynamics and oncogenesis. Front Oncol 2011;1:50
   Google Scholar
• Macůrek L, Lindqvist A, Lim D, et al. Polo-like kinase-1 is activated by aurora A to promote checkpoint recovery. Nature 2008;455(7209):119-23
   PubMed Web of Science ®Google Scholar
• Seki A, Coppinger JA, Jang CY, et al. Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry. Science 2008;320(5883):1655-8
   PubMed Web of Science ®Google Scholar
• Katayama H, Sasai K, Kawai H, et al. Phosphorylation by aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 2004;36(1):55-62
   PubMed Web of Science ®Google Scholar
• Mendez R, Murthy KG, Ryan K, et al. Phosphorylation of CPEB by Eg2 mediates the recruitment of CPSF into an active cytoplasmic polyadenylation complex. Mol Cell 2000;6(5):1253-9
   Google Scholar
• Sarkissian M, Mendez R, Richter JD. Progesterone and insulin stimulation of CPEB-dependent polyadenylation is regulated by Aurora A and glycogen synthase kinase-3. Genes Dev 2004;18(1):48-61
   Google Scholar
• Huang YS, Jung MY, Sarkissian M, Richter JD. N-methyl-D-aspartate receptor signaling results in Aurora kinase-catalyzed CPEB phosphorylation and alpha CaMKII mRNA polyadenylation at synapses. EMBO J 2002;21(9):2139-48
   Google Scholar
• Plotnikova OV, Pugacheva EN, Golemis EA. Aurora A kinase activity influences calcium signaling in kidney cells. J Cell Biol 2011;193(6):1021-32
   Google Scholar
• Yao JE, Yan M, Guan Z, et al. Aurora-A down-regulates IkappaBalpha via Akt activation and interacts with insulin-like growth factor-1 induced phosphatidylinositol 3-kinase pathway for cancer cell survival. Mol Cancer 2009;8:95
   PubMedGoogle Scholar
• Sasayama T, Marumoto T, Kunitoku N, et al. Over-expression of Aurora-A targets cytoplasmic polyadenylation element binding protein and promotes mRNA polyadenylation of Cdk1 and cyclin B1. Genes Cells 2005;10(7):627-38
   Google Scholar
• Otto T, Horn S, Brockmann M, et al. Stabilization of N-Myc is a critical function of Aurora A in human neuroblastoma. Cancer Cell 2009;15(1):67-78
   PubMed Web of Science ®Google Scholar
• Wirtz-Peitz F, Nishimura T, Knoblich JA. Linking cell cycle to asymmetric division: Aurora-A phosphorylates the Par complex to regulate Numb localization. Cell 2008;135(1):161-73
   Google Scholar
• Regan JL, Sourisseau T, Soady K, et al. Aurora A kinase regulates mammary epithelial cell fate by determining mitotic spindle orientation in a Notch-dependent manner. Cell Rep 2013;4(1):110-23
   Google Scholar
• Lee CY, Andersen RO, Cabernard C, et al. Drosophila Aurora-A kinase inhibits neuroblast self-renewal by regulating aPKC/Numb cortical polarity and spindle orientation. Genes Dev 2006;20(24):3464-74
   Google Scholar
• Lee DF, Su J, Ang YS, et al. Regulation of embryonic and induced pluripotency by aurora kinase-p53 signaling. Cell Stem Cell 2012;11(2):179-94
   Google Scholar
• Piazzolla D, Palla AR, Pantoja C, et al. Lineage-restricted function of the pluripotency factor NANOG in stratified epithelia. Nat Commun 2014;5:4226
   PubMed Web of Science ®Google Scholar
• Romain C, Paul P, Kim KW, et al. Targeting Aurora kinase-A downregulates cell proliferation and angiogenesis in neuroblastoma. J Pediatr Surg 2014;49(1):159-65
   PubMed Web of Science ®Google Scholar
• Katsha A, Soutto M, Sehdev V, et al. Aurora kinase A promotes inflammation and tumorigenesis in mice and human gastric neoplasia. Gastroenterology 2013;145(6):1312-22; e1-8
   PubMedGoogle Scholar
• Mori D, Yamada M, Mimori-Kiyosue Y, et al. An essential role of the aPKC-Aurora A-NDEL1 pathway in neurite elongation by modulation of microtubule dynamics. Nat Cell Biol 2009;11(9):1057-68
   Google Scholar
• Wu JC, Chen TY, Yu CT, et al. Identification of V23RalA-Ser194 as a critical mediator for Aurora-A-induced cellular motility and transformation by small pool expression screening. J Biol Chem 2005;280(10):9013-22
   Google Scholar
• Tsunematsu T, Takihara Y, Ishimaru N, et al. Aurora-A controls pre-replicative complex assembly and DNA replication by stabilizing geminin in mitosis. Nat Commun 2013;4:1885
   PubMed Web of Science ®Google Scholar
• Briassouli P, Chan F, Savage K, et al. Aurora-A regulation of nuclear factor-kappaB signaling by phosphorylation of IkappaBalpha. Cancer Res 2007;67(4):1689-95
   Google Scholar
• Wu CC, Yu CT, Chang GC, et al. Aurora-A promotes gefitinib resistance via a NF-kappaB signaling pathway in p53 knockdown lung cancer cells. Biochem Biophys Res Commun 2011;405(2):168-72
   Google Scholar
• Yang H, He L, Kruk P, et al. Aurora-A induces cell survival and chemoresistance by activation of Akt through a p53-dependent manner in ovarian cancer cells. Int J Cancer 2006;119(10):2304-12
   PubMed Web of Science ®Google Scholar
• Anand S, Penrhyn-Lowe S, Venkitaraman AR. AURORA-A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell 2003;3(1):51-62
   PubMed Web of Science ®Google Scholar
• Miao X, Sun T, Wang Y, et al. Functional STK15 Phe31Ile polymorphism is associated with the occurrence and advanced disease status of esophageal squamous cell carcinoma. Cancer Res 2004;64(8):2680-3
   PubMedGoogle Scholar
• Sun H, Bai J, Chen F, et al. Lack of an association between AURKA T91A polymorphisms and breast cancer: a meta-analysis involving 32,141 subjects. Breast Cancer Res Treat 2011;125(1):175-9
   PubMed Web of Science ®Google Scholar
• Bischoff JR, Anderson L, Zhu Y, et al. A homologue of Drosophila aurora kinase is oncogenic and amplified in human colorectal cancers. EMBO J 1998;17(11):3052-65
   PubMed Web of Science ®Google Scholar
• Zhou H, Kuang J, Zhong L, et al. Tumour amplified kinase STK15/BTAK induces centrosome amplification, aneuploidy and transformation. Nat Genet 1998;20(2):189-93
   PubMed Web of Science ®Google Scholar
• Tatsuka M, Sato S, Kitajima S, et al. Overexpression of Aurora-A potentiates HRAS-mediated oncogenic transformation and is implicated in oral carcinogenesis. Oncogene 2005;24(6):1122-7
   Google Scholar
• Wang X, Zhou YX, Qiao W, et al. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene 2006;25(54):7148-58
   Google Scholar
• Zhang D, Hirota T, Marumoto T, et al. Cre-loxP-controlled periodic Aurora-A overexpression induces mitotic abnormalities and hyperplasia in mammary glands of mouse models. Oncogene 2004;23(54):8720-30
   Google Scholar
• Wang H, Somers GW, Bashirullah A, et al. Aurora-A acts as a tumor suppressor and regulates self-renewal of Drosophila neuroblasts. Genes Dev 2006;20(24):3453-63
   Google Scholar
• Carter SL, Eklund AC, Kohane IS, et al. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Nat Genet 2006;38(9):1043-8
   PubMed Web of Science ®Google Scholar
• Meraldi P, Honda R, Nigg EA. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J 2002;21(4):483-92
   Google Scholar
• Mao JH, Wu D, Perez-Losada J, et al. Crosstalk between Aurora-A and p53: frequent deletion or downregulation of Aurora-A in tumors from p53 null mice. Cancer Cell 2007;11(2):161-73
   Google Scholar
• Giubettini M, Asteriti IA, Scrofani J, et al. Control of Aurora-A stability through interaction with TPX2. J Cell Sci 2011;124(Pt 1):113-22
   PubMed Web of Science ®Google Scholar
• Perez de Castro I, Malumbres M. Mitotic stress and chromosomal instability in cancer: the case for TPX2. Genes Cancer 2012;3(11-12):721-30
   Google Scholar
• Asteriti IA, Rensen WM, Lindon C, et al. The Aurora-A/TPX2 complex: a novel oncogenic holoenzyme? Biochim Biophys Acta 2010;1806(2):230-9
   Google Scholar
• Burum-Auensen E, De Angelis PM, Schjølberg AR, et al. Subcellular localization of the spindle proteins Aurora A, Mad2, and BUBR1 assessed by immunohistochemistry. J Histochem Cytochem 2007;55(5):477-86
   Google Scholar
• Lim KH, Brady DC, Kashatus DF, et al. Aurora-A phosphorylates, activates, and relocalizes the small GTPase RalA. Mol Cell Biol 2010;30(2):508-23
   PubMedGoogle Scholar
• Dimova I, Raitcheva S, Dimitrov R, et al. Correlations between c-myc gene copy-number and clinicopathological parameters of ovarian tumours. Eur J Cancer 2006;42(5):674-9
   Google Scholar
• Giet R, Prigent C. The Xenopus laevis aurora/Ip11p-related kinase pEg2 participates in the stability of the bipolar mitotic spindle. Exp Cell Res 2000;258(1):145-51
   Google Scholar
• Hannak E, Kirkham M, Hyman AA, Oegema K. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol 2001;155(7):1109-16
   Google Scholar
• Roghi C, Giet R, Uzbekov R, et al. The Xenopus protein kinase pEg2 associates with the centrosome in a cell cycle-dependent manner, binds to the spindle microtubules and is involved in bipolar mitotic spindle assembly. J Cell Sci 1998;111(Pt 5):557-72
   Google Scholar
• Schumacher JM, Ashcroft N, Donovan PJ, Golden A. A highly conserved centrosomal kinase, AIR-1, is required for accurate cell cycle progression and segregation of developmental factors in Caenorhabditis elegans embryos. Development 1998;125(22):4391-402
   Google Scholar
• Du J, Hannon GJ. Suppression of p160ROCK bypasses cell cycle arrest after Aurora-A/STK15 depletion. Proc Natl Acad Sci USA 2004;101(24):8975-80
   Google Scholar
• Kunitoku N, Sasayama T, Marumoto T, et al. CENP-A phosphorylation by Aurora-A in prophase is required for enrichment of Aurora-B at inner centromeres and for kinetochore function. Dev Cell 2003;5(6):853-64
   Google Scholar
• Perez de Castro I, Aguirre-Portoles C, Fernandez-Miranda G, et al. Requirements for Aurora-A in tissue regeneration and tumor development in adult mammals. Cancer Res 2013;73(23):6804-15
   Google Scholar
• Cheung CH, Coumar MS, Chang JY, Hsieh HP. Aurora kinase inhibitor patents and agents in clinical testing: an update (2009-10). Expert Opin Ther Pat 2011;21(6):857-84
   PubMed Web of Science ®Google Scholar
• Coumar MS, Cheung CH, Chang JY, Hsieh HP. Advances in Aurora kinase inhibitor patents. Expert Opin Ther Pat 2009;19(3):321-56
   Web of Science ®Google Scholar
• Cheung CH, Coumar MS, Hsieh HP, Chang JY. Aurora kinase inhibitors in preclinical and clinical testing. Expert Opin Investig Drugs 2009;18(4):379-98
   PubMed Web of Science ®Google Scholar
• Green MR, Woolery JE, Mahadevan D. Update on Aurora kinase targeted therapeutics in oncology. Expert Opin Drug Discov 2011;6(3):291-307
   PubMed Web of Science ®Google Scholar
• Wang X, Sinn AL, Pollok K, et al. Preclinical activity of a novel multiple tyrosine kinase and aurora kinase inhibitor, ENMD-2076, against multiple myeloma. Br J Haematol 2010;150(3):313-25
   Google Scholar
• Tentler JJ, Bradshaw-Pierce EL, Serkova NJ, et al. Assessment of the in vivo antitumor effects of ENMD-2076, a novel multitargeted kinase inhibitor, against primary and cell line-derived human colorectal cancer xenograft models. Clin Cancer Res 2010;16(11):2989-98
   Google Scholar
• Fletcher GC, Brokx RD, Denny TA, et al. ENMD-2076 is an orally active kinase inhibitor with antiangiogenic and antiproliferative mechanisms of action. Mol Cancer Ther 2011;10(1):126-37
   PubMed Web of Science ®Google Scholar
• Diamond JR, Bastos BR, Hansen RJ, et al. Phase I safety, pharmacokinetic, and pharmacodynamic study of ENMD-2076, a novel angiogenic and Aurora kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2011;17(4):849-60
   PubMed Web of Science ®Google Scholar
• Matulonis UA, Lee J, Lasonde B, et al. ENMD-2076, an oral inhibitor of angiogenic and proliferation kinases, has activity in recurrent, platinum resistant ovarian cancer. Eur J Cancer 2013;49(1):121-31
   PubMed Web of Science ®Google Scholar
• Diamond JR, Eckhardt SG, Tan AC, et al. Predictive biomarkers of sensitivity to the aurora and angiogenic kinase inhibitor ENMD-2076 in preclinical breast cancer models. Clin Cancer Res 2013;19(1):291-303
   PubMed Web of Science ®Google Scholar
• Shiomitsu K, Sajo E, Rubin C, Sehgal I. The radiosensitizing effect of the aurora kinase inhibitors, ENMD-2076, on canine mast cell tumours in vitro. Vet Comp Oncol 2013. [Epub ahead of print]
   Google Scholar
• Shimomura T, Hasako S, Nakatsuru Y, et al. MK-5108, a highly selective Aurora-A kinase inhibitor, shows antitumor activity alone and in combination with docetaxel. Mol Cancer Ther 2010;9(1):157-66
   PubMedGoogle Scholar
• Chefetz I, Holmberg JC, Alvero AB, et al. Inhibition of Aurora-A kinase induces cell cycle arrest in epithelial ovarian cancer stem cells by affecting NFκB pathway. Cell Cycle 2011;10(13):2206-14
   PubMed Web of Science ®Google Scholar
• Shan W, Akinfenwa PY, Savannah KB, et al. A small-molecule inhibitor targeting the mitotic spindle checkpoint impairs the growth of uterine leiomyosarcoma. Clin Cancer Res 2012;18(12):3352-65
   PubMed Web of Science ®Google Scholar
• Chinn DC, Holland WS, Mack PC. Anticancer activity of the Aurora A kinase inhibitor MK-5108 in non-small-cell lung cancer (NSCLC) in vitro as monotherapy and in combination with chemotherapies. J Cancer Res Clin Oncol 2014;140(7):1137-49
   Google Scholar
• Horwacik I, Durbas M, Boratyn E, et al. Targeting GD2 ganglioside and aurora A kinase as a dual strategy leading to cell death in cultures of human neuroblastoma cells. Cancer Lett 2013;341(2):248-64
   PubMed Web of Science ®Google Scholar
• Kretzner L, Scuto A, Dino PM, et al. Combining histone deacetylase inhibitor vorinostat with aurora kinase inhibitors enhances lymphoma cell killing with repression of c-Myc, hTERT, and microRNA levels. Cancer Res 2011;71(11):3912-20
   PubMed Web of Science ®Google Scholar
• Minton S, LoRusso P, Lockhart A, et al. A phase I study of MK-5108, an oral aurora A kinase inhibitor, in both monotherapy and in combination with docetaxel in patients with advanced solid tumors. J Clin Oncol 2010;28(15_Suppl):abstract e13026
   Google Scholar
• Manfredi MG, Ecsedy JA, Meetze KA, et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci USA 2007;104(10):4106-11
   PubMedGoogle Scholar
• Shang X, Burlingame SM, Okcu MF, et al. Aurora A is a negative prognostic factor and a new therapeutic target in human neuroblastoma. Mol Cancer Ther 2009;8(8):2461-9
   PubMed Web of Science ®Google Scholar
• Hoar K, Chakravarty A, Rabino C, et al. MLN8054, a small-molecule inhibitor of Aurora A, causes spindle pole and chromosome congression defects leading to aneuploidy. Mol Cell Biol 2007;27(12):4513-25
   PubMed Web of Science ®Google Scholar
• Chakravarty A, Shinde V, Tabernero J, et al. Phase I assessment of new mechanism-based pharmacodynamic biomarkers for MLN8054, a small-molecule inhibitor of Aurora A kinase. Cancer Res 2011;71(3):675-85
   PubMed Web of Science ®Google Scholar
• Dar AA, Belkhiri A, Ecsedy J, et al. Aurora kinase A inhibition leads to p73-dependent apoptosis in p53-deficient cancer cells. Cancer Res 2008;68(21):8998-9004
   PubMed Web of Science ®Google Scholar
• Huck JJ, Zhang M, McDonald A, et al. MLN8054, an inhibitor of Aurora A kinase, induces senescence in human tumor cells both in vitro and in vivo. Mol Cancer Res 2010;8(3):373-84
   Google Scholar
• Macarulla T, Cervantes A, Elez E, et al. Phase I study of the selective Aurora A kinase inhibitor MLN8054 in patients with advanced solid tumors: safety, pharmacokinetics, and pharmacodynamics. Mol Cancer Ther 2010;9(10):2844-52
   PubMed Web of Science ®Google Scholar
• Dees EC, Infante JR, Cohen RB, et al. Phase 1 study of MLN8054, a selective inhibitor of Aurora A kinase in patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67(4):945-54
   PubMed Web of Science ®Google Scholar
• Manfredi MG, Ecsedy JA, Chakravarty A, et al. Characterization of Alisertib (MLN8237), an investigational small-molecule inhibitor of aurora A kinase using novel in vivo pharmacodynamic assays. Clin Cancer Res 2011;17(24):7614-24
   PubMed Web of Science ®Google Scholar
• Qi W, Spier C, Liu X, et al. Alisertib (MLN8237) an investigational agent suppresses Aurora A and B activity, inhibits proliferation, promotes endo-reduplication and induces apoptosis in T-NHL cell lines supporting its importance in PTCL treatment. Leuk Res 2013;37(4):434-9
   PubMed Web of Science ®Google Scholar
• Tomita M, Mori N. Aurora A selective inhibitor MLN8237 suppresses the growth and survival of HTLV-1-infected T-cells in vitro. Cancer Sci 2010;101(5):1204-11
   Google Scholar
• Wen Q, Goldenson B, Silver SJ, et al. Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL. Cell 2012;150(3):575-89
   PubMed Web of Science ®Google Scholar
• Görgün G, Calabrese E, Hideshima T, et al. A novel Aurora-A kinase inhibitor MLN8237 induces cytotoxicity and cell-cycle arrest in multiple myeloma. Blood 2010;115(25):5202-13
   PubMed Web of Science ®Google Scholar
• Do TV, Xiao F, Bickel LE, et al. Aurora kinase A mediates epithelial ovarian cancer cell migration and adhesion. Oncogene 2014;33(5):539-49
   Google Scholar
• Zhou N, Singh K, Mir MC, et al. The investigational Aurora kinase A inhibitor MLN8237 induces defects in cell viability and cell-cycle progression in malignant bladder cancer cells in vitro and in vivo. Clin Cancer Res 2013;19(7):1717-28
   PubMed Web of Science ®Google Scholar
• Patel AV, Eaves D, Jessen WJ, et al. Ras-driven transcriptome analysis identifies aurora kinase A as a potential malignant peripheral nerve sheath tumor therapeutic target. Clin Cancer Res 2012;18(18):5020-30
   PubMed Web of Science ®Google Scholar
• Asteriti IA, Giubettini M, Lavia P, Guarguaglini G. Aurora-A inactivation causes mitotic spindle pole fragmentation by unbalancing microtubule-generated forces. Mol Cancer 2011;10:131
   PubMed Web of Science ®Google Scholar
• Liu Y, Hawkins OE, Su Y, et al. Targeting aurora kinases limits tumour growth through DNA damage-mediated senescence and blockade of NF-kappaB impairs this drug-induced senescence. EMBO Mol Med 2013;5(1):149-66
   Google Scholar
• Lehman NL, O’Donnell JP, Whiteley LJ, et al. Aurora A is differentially expressed in gliomas, is associated with patient survival in glioblastoma and is a potential chemotherapeutic target in gliomas. Cell Cycle 2012;11(3):489-502
   PubMed Web of Science ®Google Scholar
• Marxer M, Ma HT, Man WY, Poon RY. p53 deficiency enhances mitotic arrest and slippage induced by pharmacological inhibition of Aurora kinases. Oncogene 2014;33(27):3550-60
   Google Scholar
• Neel NF, Stratford JK, Shinde V, et al. Response to MLN8237 in pancreatic cancer is not dependent on RalA phosphorylation. Mol Cancer Ther 2014;13(1):122-33
   Google Scholar
• Kelly KR, Ecsedy J, Medina E, et al. The novel Aurora A kinase inhibitor MLN8237 is active in resistant chronic myeloid leukaemia and significantly increases the efficacy of nilotinib. J Cell Mol Med 2011;15(10):2057-70
   Google Scholar
• Kelly KR, Nawrocki ST, Espitia CM, et al. Targeting Aurora A kinase activity with the investigational agent alisertib increases the efficacy of cytarabine through a FOXO-dependent mechanism. Int J Cancer 2012;131(11):2693-703
   PubMed Web of Science ®Google Scholar
• Qi W, Cooke LS, Liu X, et al. Aurora inhibitor MLN8237 in combination with docetaxel enhances apoptosis and anti-tumor activity in mantle cell lymphoma. Biochem Pharmacol 2011;81(7):881-90
   PubMed Web of Science ®Google Scholar
• Sehdev V, Katsha A, Ecsedy J, et al. The combination of alisertib, an investigational Aurora kinase A inhibitor, and docetaxel promotes cell death and reduces tumor growth in preclinical cell models of upper gastrointestinal adenocarcinomas. Cancer 2013;119(4):904-14
   Google Scholar
• Venkataraman S, Alimova I, Tello T, et al. Targeting Aurora Kinase A enhances radiation sensitivity of atypical teratoid rhabdoid tumor cells. J Neurooncol 2012;107(3):517-26
   PubMed Web of Science ®Google Scholar
• Brewer Savannah KJ, Demicco EG, Lusby K, et al. Dual targeting of mTOR and aurora-A kinase for the treatment of uterine Leiomyosarcoma. Clin Cancer Res 2012;18(17):4633-45
   PubMed Web of Science ®Google Scholar
• Mahadevan D, Stejskal A, Cooke LS, et al. Aurora A inhibitor (MLN8237) plus vincristine plus rituximab is synthetic lethal and a potential curative therapy in aggressive B-cell non-Hodgkin lymphoma. Clin Cancer Res 2012;18(8):2210-19
   PubMed Web of Science ®Google Scholar
• Sehdev V, Peng D, Soutto M, et al. The aurora kinase A inhibitor MLN8237 enhances cisplatin-induced cell death in esophageal adenocarcinoma cells. Mol Cancer Ther 2012;11(3):763-74
   Google Scholar
• Muscal JA, Scorsone KA, Zhang L, et al. Additive effects of vorinostat and MLN8237 in pediatric leukemia, medulloblastoma, and neuroblastoma cell lines. Invest New Drugs 2013;31(1):39-45
   PubMed Web of Science ®Google Scholar
• Dees EC, Cohen RB, von Mehren M, et al. Phase I study of aurora A kinase inhibitor MLN8237 in advanced solid tumors: safety, pharmacokinetics, pharmacodynamics, and bioavailability of two oral formulations. Clin Cancer Res 2012;18(17):4775-84
   PubMed Web of Science ®Google Scholar
• Cervantes A, Elez E, Roda D, et al. Phase I pharmacokinetic/pharmacodynamic study of MLN8237, an investigational, oral, selective aurora a kinase inhibitor, in patients with advanced solid tumors. Clin Cancer Res 2012;18(17):4764-74
   PubMed Web of Science ®Google Scholar
• Mossé YP, Lipsitz E, Fox E, et al. Pediatric phase I trial and pharmacokinetic study of MLN8237, an investigational oral selective small-molecule inhibitor of Aurora kinase A: a Children’s Oncology Group Phase I Consortium study. Clin Cancer Res 2012;18(21):6058-64
   PubMed Web of Science ®Google Scholar
• Kelly KR, Shea TC, Goy A, et al. Phase I study of MLN8237-investigational Aurora A kinase inhibitor-in relapsed/refractory multiple myeloma, Non-Hodgkin lymphoma and chronic lymphocytic leukemia. Invest New Drugs 2014;32(3):489-99
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Mahadevan D, Cebula E, et al. Phase II study of alisertib, a selective Aurora A kinase inhibitor, in relapsed and refractory aggressive B- and T-cell non-Hodgkin lymphomas. J Clin Oncol 2014;32(1):44-50
   PubMed Web of Science ®Google Scholar
• Matulonis UA, Sharma S, Ghamande S, et al. Phase II study of MLN8237 (alisertib), an investigational Aurora A kinase inhibitor, in patients with platinum-resistant or -refractory epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Gynecol Oncol 2012;127(1):63-9
   PubMed Web of Science ®Google Scholar
• Hrabakova R, Kollareddy M, Tyleckova J, et al. Cancer cell resistance to aurora kinase inhibitors: identification of novel targets for cancer therapy. J Proteome Res 2013;12(1):455-69
   Google Scholar
• Zou Z, Yuan Z, Zhang Q, et al. Aurora kinase A inhibition-induced autophagy triggers drug resistance in breast cancer cells. Autophagy 2012;8(12):1798-810
   PubMed Web of Science ®Google Scholar
• Kesisova IA, Nakos KC, Tsolou A, et al. Tripolin A, a novel small-molecule inhibitor of aurora A kinase, reveals new regulation of HURP’s distribution on microtubules. PLoS One 2013;8(3):e58485
   PubMed Web of Science ®Google Scholar
• Palani S, Patel M, Huck J, et al. Preclinical pharmacokinetic/pharmacodynamic/efficacy relationships for alisertib, an investigational small-molecule inhibitor of Aurora A kinase. Cancer Chemother Pharmacol 2013;72(6):1255-64
   PubMed Web of Science ®Google Scholar
• Jeon HY, Lee H. Depletion of Aurora-A in zebrafish causes growth retardation due to mitotic delay and p53-dependent cell death. FEBS J 2013;280(6):1518-30
   Google Scholar
• Zhao B, Smallwood A, Yang J, et al. Modulation of kinase-inhibitor interactions by auxiliary protein binding: crystallography studies on Aurora A interactions with VX-680 and with TPX2. Protein Sci 2008;17(10):1791-7
   Google Scholar
• Ice RJ, McLaughlin SL, Livengood RH, et al. NEDD9 depletion destabilizes Aurora A kinase and heightens the efficacy of Aurora A inhibitors: implications for treatment of metastatic solid tumors. Cancer Res 2013;73(10):3168-80
   Google Scholar
• Shionome Y, Lin WH, Shiao HY, et al. A novel aurora-A inhibitor, BPR1K0609S1, sensitizes colorectal tumor cells to 5-fluorofracil (5-FU) treatment. Int J Biol Sci 2013;9(4):403-11
   Google Scholar
• Tang YC, Williams BR, Siegel JJ, Amon A. Identification of aneuploidy-selective antiproliferation compounds. Cell 2011;144(4):499-512
   PubMed Web of Science ®Google Scholar
• Toledo LI, Murga M, Zur R, et al. A cell-based screen identifies ATR inhibitors with synthetic lethal properties for cancer-associated mutations. Nat Struct Mol Biol 2011;18(6):721-7
   PubMed Web of Science ®Google Scholar
• Siggelkow W, Boehm D, Gebhard S, et al. Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients. BMC Cancer 2012;12:562
   PubMed Web of Science ®Google Scholar
• Nadler Y, Camp RL, Schwartz C, et al. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Clin Cancer Res 2008;14(14):4455-62
   PubMed Web of Science ®Google Scholar
• Staff S, Isola J, Jumppanen M, Tanner M. Aurora-A gene is frequently amplified in basal-like breast cancer. Oncol Rep 2010;23(2):307-12
   PubMed Web of Science ®Google Scholar
• Miyoshi Y, Iwao K, Egawa C, Noguchi S. Association of centrosomal kinase STK15/BTAK mRNA expression with chromosomal instability in human breast cancers. Int J Cancer 2001;92(3):370-3
   PubMed Web of Science ®Google Scholar
• Goos JA, Coupe VM, Diosdado B, et al. Aurora kinase A (AURKA) expression in colorectal cancer liver metastasis is associated with poor prognosis. Br J Cancer 2013;109(9):2445-52
   PubMed Web of Science ®Google Scholar
• Dotan E, Meropol NJ, Zhu F, et al. Relationship of increased aurora kinase A gene copy number, prognosis and response to chemotherapy in patients with metastatic colorectal cancer. Br J Cancer 2012;106(4):748-55
   Google Scholar
• Sakakura C, Hagiwara A, Yasuoka R, et al. Tumour-amplified kinase BTAK is amplified and overexpressed in gastric cancers with possible involvement in aneuploid formation. Br J Cancer 2001;84(6):824-31
   PubMed Web of Science ®Google Scholar
• Yen CC, Yeh CN, Cheng CT, et al. Integrating bioinformatics and clinicopathological research of gastrointestinal stromal tumors: identification of aurora kinase A as a poor risk marker. Ann Surg Oncol 2012;19(11):3491-9
   Google Scholar
• Reiter R, Gais P, Jütting U, et al. Aurora kinase A messenger RNA overexpression is correlated with tumor progression and shortened survival in head and neck squamous cell carcinoma. Clin Cancer Res 2006;12(17):5136-41
   PubMed Web of Science ®Google Scholar
• Tatsuka M, Sato S, Kanda A, et al. Oncogenic role of nuclear accumulated Aurora-A. Mol Carcinog 2009;48(9):810-20
   Google Scholar
• Kitajima S, Kudo Y, Ogawa I, et al. Constitutive phosphorylation of aurora-a on ser51 induces its stabilization and consequent overexpression in cancer. PLoS One 2007;2(9):e944
   Google Scholar
• Camacho E, Beà S, Salaverría I, et al. Analysis of Aurora-A and hMPS1 mitotic kinases in mantle cell lymphoma. Int J Cancer 2006;118(2):357-63
   Google Scholar
• Inamdar KV, O’Brien S, Sen S, et al. Aurora-A kinase nuclear expression in chronic lymphocytic leukemia. Mod Pathol 2008;21(12):1428-35
   Google Scholar
• Lucena-Araujo AR, de Oliveira FM, Leite-Cueva SD, et al. High expression of AURKA and AURKB is associated with unfavorable cytogenetic abnormalities and high white blood cell count in patients with acute myeloid leukemia. Leuk Res 2011;35(2):260-4
   PubMed Web of Science ®Google Scholar
• Xu HT, Ma L, Qi FJ, et al. Expression of serine threonine kinase 15 is associated with poor differentiation in lung squamous cell carcinoma and adenocarcinoma. Pathol Int 2006;56(7):375-80
   PubMed Web of Science ®Google Scholar
• Ogawa E, Takenaka K, Katakura H, et al. Perimembrane Aurora-A expression is a significant prognostic factor in correlation with proliferative activity in non-small-cell lung cancer (NSCLC). Ann Surg Oncol 2008;15(2):547-54
   Google Scholar
• Lo Iacono M, Monica V, Saviozzi S, et al. Aurora Kinase A expression is associated with lung cancer histological-subtypes and with tumor de-differentiation. J Transl Med 2011;9:100
   Google Scholar
• Neben K, Korshunov A, Benner A, et al. Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival. Cancer Res 2004;64(9):3103-11
   PubMed Web of Science ®Google Scholar
• Reichardt W, Jung V, Brunner C, et al. The putative serine/threonine kinase gene STK15 on chromosome 20q13.2 is amplified in human gliomas. Oncol Rep 10(5):1275-9
   Google Scholar
• Klein A, Reichardt W, Jung V, et al. Overexpression and amplification of STK15 in human gliomas. Int J Oncol 2004;25(6):1789-94
   Google Scholar
• Moreno-Bueno G, Sánchez-Estévez C, Cassia R, et al. Differential gene expression profile in endometrioid and nonendometrioid endometrial carcinoma: STK15 is frequently overexpressed and amplified in nonendometrioid carcinomas. Cancer Res 2003;63(18):5697-702
   Google Scholar
• Gritsko TM, Coppola D, Paciga JE, et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Res 2003;9(4):1420-6
   PubMed Web of Science ®Google Scholar
• Landen CN, Lin YG, Immaneni A, et al. Overexpression of the centrosomal protein Aurora-A kinase is associated with poor prognosis in epithelial ovarian cancer patients. Clin Cancer Res 2007;13(14):4098-104
   PubMed Web of Science ®Google Scholar
• Lassus H, Staff S, Leminen A, et al. Aurora-A overexpression and aneuploidy predict poor outcome in serous ovarian carcinoma. Gynecol Oncol 2011;120(1):11-17
   Google Scholar
• Mendiola M, Barriuso J, Mariño-Enríquez A, et al. Aurora kinases as prognostic biomarkers in ovarian carcinoma. Hum Pathol 2009;40(5):631-8
   Google Scholar
• Li D, Zhu J, Firozi PF, et al. Overexpression of oncogenic STK15/BTAK/Aurora A kinase in human pancreatic cancer. Clin Cancer Res 2003;9(3):991-7
   PubMed Web of Science ®Google Scholar
• Zhu J, Abbruzzese JL, Izzo J, et al. AURKA amplification, chromosome instability, and centrosome abnormality in human pancreatic carcinoma cells. Cancer Genet Cytogenet 2005;159(1):10-17
   Google Scholar
• Bar-Shira A, Pinthus JH, Rozovsky U, et al. Multiple genes in human 20q13 chromosomal region are involved in an advanced prostate cancer xenograft. Cancer Res 2002;62(23):6803-7
   PubMed Web of Science ®Google Scholar
• Buschhorn HM, Klein RR, Chambers SM, et al. Aurora-A over-expression in high-grade PIN lesions and prostate cancer. Prostate 2005;64(4):341-6
   PubMed Web of Science ®Google Scholar
• Torchia EC, Chen Y, Sheng H, et al. A genetic variant of Aurora kinase A promotes genomic instability leading to highly malignant skin tumors. Cancer Res 2009;69(18):7207-15
   Google Scholar
• Sen S, Zhou H, Zhang RD, et al. Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 2002;94(17):1320-9
   Google Scholar
• Lei Y, Yan S, Ming-De L, et al. Prognostic significance of Aurora-A expression in human bladder cancer. Acta Histochem 2011;113(5):514-18
   PubMed Web of Science ®Google Scholar
• Bufo P, Sanguedolce F, Tortorella S, et al. Expression of mitotic kinases phospho-aurora A and aurora B correlates with clinical and pathological parameters in bladder neoplasms. Histol Histopathol 2010;25(11):1371-7
   Google Scholar
• Giet R, McLean D, Descamps S, et al. Drosophila Aurora A kinase is required to localize D-TACC to centrosomes and to regulate astral microtubules. J Cell Biol 2002;156(3):437-51
   Google Scholar
• Furuta T, Baillie DL, Schumacher JM. Caenorhabditis elegans Aurora A kinase AIR-1 is required for postembryonic cell divisions and germline development. Genesis 2002;34(4):244-50
   Google Scholar
• Liu Q, Ruderman JV. Aurora A, mitotic entry, and spindle bipolarity. Proc Natl Acad Sci USA 2006;103(15):5811-16
   PubMed Web of Science ®Google Scholar
• Yang H, Burke T, Dempsey J, et al. Mitotic requirement for aurora A kinase is bypassed in the absence of aurora B kinase. FEBS Lett 2005;579(16):3385-91
   Google Scholar
• Pratz KW, Cortes J, Roboz GJ, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood 2009;113(17):3938-46
   PubMed Web of Science ®Google Scholar
• Traynor AM, Hewitt M, Liu G, et al. Phase I dose escalation study of MK-0457, a novel Aurora kinase inhibitor, in adult patients with advanced solid tumors. Cancer Chemother Pharmacol 2011;67(2):305-14
   PubMed Web of Science ®Google Scholar
• Giles FJ, Swords RT, Nagler A, et al. MK-0457, an Aurora kinase and BCR-ABL inhibitor, is active in patients with BCR-ABL T315I leukemia. Leukemia 2013;27(1):113-17
   PubMed Web of Science ®Google Scholar
• Meulenbeld HJ, Bleuse JP, Vinci EM, et al. Randomized phase II study of danusertib in patients with metastatic castration-resistant prostate cancer after docetaxel failure. BJU Int 2013;111(1):44-52
   PubMed Web of Science ®Google Scholar
• Dent SF, Gelmon KA, Chi KN, et al. NCIC CTG IND.181: phase I study of AT9283 given as a weekly 24 hour infusion in advanced malignancies. Invest New Drugs 2013;31(6):1522-9
   Google Scholar
• Foran J, Ravandi F, Wierda W, et al. A phase I and pharmacodynamic study of AT9283, a small-molecule inhibitor of aurora kinases in patients with relapsed/refractory leukemia or myelofibrosis. Clin Lymphoma Myeloma Leuk 2014;14(3):223-30
   PubMedGoogle Scholar
• Arkenau HT, Plummer R, Molife LR, et al. A phase I dose escalation study of AT9283, a small molecule inhibitor of aurora kinases, in patients with advanced solid malignancies. Ann Oncol 2012;23(5):1307-13
   PubMedGoogle Scholar
• Schöffski P, Jones SF, Dumez H, et al. Phase I, open-label, multicentre, dose-escalation, pharmacokinetic and pharmacodynamic trial of the oral aurora kinase inhibitor PF-03814735 in advanced solid tumours. Eur J Cancer 2011;47(15):2256-64
   Google Scholar