Aurora kinase inhibitors: Identification and preclinical validation of their biomarkers

Expert Opinion on Therapeutic Targets

Volumn 12, Issue 1, 2008, Pages 69-80

  Carpinelli, Patrizia ^a   Moll, Jürgen ^a  

^a NERVIANO MEDICAL SCIENCES   (Italy)

Author keywords

Aurora kinases; Biomarkers; Cancer; Small molecule inhibitors

Indexed keywords

ANTINEOPLASTIC AGENT; AS 703569; AT 9283; AURORA A KINASE; AURORA B KINASE; AURORA KINASE INHIBITOR; AZD 1152; BIOLOGICAL MARKER; CYC 116; CYCLOPROPANECARBOXYLIC ACID [4 [4 (4 METHYL 1 PIPERAZINYL) 6 (5 METHYL 2H PYRAZOL 3 YLAMINO) 2 PYRIMIDINYLTHIO]PHENYL]AMIDE; HISTONE H3; MLN 8054; PF 03814735; PHA 680632; PHA 739358; PROTEIN P53; R 763; UNCLASSIFIED DRUG; VX 667;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; AUTOPHOSPHORYLATION; CHRONIC MYELOID LEUKEMIA; CLINICAL TRIAL; DOSE TIME EFFECT RELATION; DRUG BLOOD LEVEL; DRUG IDENTIFICATION; DRUG POTENCY; DRUG RESEARCH; DRUG SELECTIVITY; ENZYME ACTIVITY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; ENZYME SUBSTRATE COMPLEX; HUMAN; NONHUMAN; PHARMACODYNAMICS; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; REVIEW; SIGNAL TRANSDUCTION; SOLID TUMOR; VALIDATION PROCESS;

ANIMALS; BIOLOGICAL MARKERS; DRUG EVALUATION, PRECLINICAL; HUMANS; PROTEIN KINASE INHIBITORS; PROTEIN-SERINE-THREONINE KINASES; REPRODUCIBILITY OF RESULTS;

EID: 39049166077     PISSN: 14728222     EISSN: None     Source Type: Journal    
DOI: 10.1517/14728222.12.1.69     Document Type: Review

References (91)

1. Frank R, Hargreaves R. Clinical biomarkers in drug discovery and development. Nat Rev Drug Discov 2003;2(7):566-80
2. Ludwig JA, Weinstein JN. Biomarkers in cancer staging, prognosis and treatment selection. Nat Rev Cancer 2005;5(11):845-56
3. Manne U, Srivastava RG, Srivastava S. Recent advances in biomarkers for cancer diagnosis and treatment. Drug Discov Today 2005;10(14):965-76
4. 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
5. Pugacheva EN, Golemis EA. HEF1-Aurora A interactions: points of dialog between the cell cycle and cell attachment signaling networks. Cell Cycle 2006;5(4):384-91
6. Briassouli P, Chan F, Savage K, et al. Aurora-A regulation of nuclear factor-κB signaling by phosphorylation of IκBα. Cancer Res 2007;67(4):1689-95
7. Girdler F, Gascoigne KE, Eyers PA, et al. Validating Aurora B as an anti-cancer drug target. J Cell Sci 2006;119(Pt 17):3664-75
8. Li JJ, Li SA. Mitotic kinases: the key to duplication, segregation, and cytokinesis errors, chromosomal instability and oncogenesis. Pharmacol Ther 2006;111(3):974-84
9. Sen S, Zhou H, White RA. A putative serine/threonine kinaae encoding gene BTAK on chromosome 20q13 is amplified and overexpressed in human breast cancer cell lines. Oncogene 1997;14(18):2195-200
10. 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
11. Gritsko TM, Coppola D, Paciga JE, et al. Activation and overexpression of centrosome kinase BTAK/Aurora-A in human ovarian cancer. Clin Cancer Ret 2003;9(4):1420-6
12. 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
13. 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
14. Neben K, Korshunov A, Benner A, et al. Microarray-based screening for molecular markers in medulloblastoma revealed STK15 as independent predictor for survival. Cancer Ret 2004;64(9):3103-11
15. 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
16. Ewart-Toland A, Dai Q, Gao YT, et al. Aurora-A/STK15 T+91A is a general low penetrance cancer susceptibility gene: a meta-analysis of multiple cancer types. Carcinogenesis 2005;26(8):1368-73
17. 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
18. 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
19. Adams RR, Carmena M, Earnshaw WC. Chromosomal passengers and the (Aurora) ABCs of mitosis. Trends Cell Biol 2001;11(2):49-54
20. Adams RR, Maiato H, Earnshaw WC, Carmena M. Essential roles of Drosophila inner centromere protein (INCENP) and Aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol 2001;153(4):865
21. Carvajal RD, Tse A, Schwartz GK. Aurora kinases: new targets for cancer therapy. Clin Cancer Ret 2006;12(23):6869-75
22. Carmena M, Earnshaw WC. The cellular geography of Aurora kinases. Nat Rev Mol Cell Biol 2003;4(11):842-54
23. Sasai K, Katayama H, Stenoien DL, et al. Aurora-C kinase is a novel chromosomal passenger protein that can complement Aurora-B kinase function in mitotic cells. Cell Motil Cytoskeleton 2004;59(4):249-63
24. Greenman C, Stephens P. Smith R, et al. Patterns of somatic mutation in human cancer genomes. Nature 2007;446(7132):153-8
25. Davies H, Hunter C, Smith R, et al. Somatic mutations of the protein kinase gene family in human lung cancer. Cancer Ret 2005;65(17):7591-5
26. Jeng YM, Peng SY, Lin CY, Hsu HC. Overexpression and amplification of Aurora-A in hepatocellular carcinoma. Clin Cancer Ret 2004;10(6):2065-71
27. Ditchfield C, Johnson VL, Tighe A, et al. Aurora B couples chromosome alignment with anaphase by targeting BubR1, Mad2, and Cenp-E to kinetochores. J Cell Biol 2003;161(2):267-80
28. Marumoto T, Honda S, Hara T, et al. Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem 2003;278(51):51786-95
29. Hauf S, Cole RW, Laterra S, et al. The small molecule hesperadin reveals a role for Aurora B in correcting kinetochore-microtubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol 2003;161(2):281-94
30. Harrington EA, Bebbington D, Moore J, et al. VX-680, a potent and selective small-molecule inhibitor of the Aurora kinases, suppresses tumor growth in vivo. Nat Med 2004;10(3):262-7
31. Soncini C, Carpinelli P, Gianellini L, et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Ret 2006;12(13):4080-9
32. Wilkinson RW, Odedra R, Heaton SP, et al. AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res 2007;13(12):3682-8
33. Fancelli D, Moll J, Varasi M, et al. 1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles: identification of a potent Aurora kinase inhibitor with a favorable antitumor kinase inhibition profile. J Med Chem 2006;49(24):7247-51
34. 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
35. Walter AO, Seghezzi W, Korver W, et al. The mitotic serine/threonine kinase Aurora2/AIK is regulated by phosphorylation and degradation. Oncogene 2000;19(42):4906-16
36. Katayama H, Zhou H, Li Q, et al. Interaction and feedback regulation between STK15/BTAK/Aurora-A kinase and protein phosphatase 1 through mitotic cell division cycle. J Biol Chem 2001;276(49):46219-24
37. Kufer TA, Sillje HH, Korner R, et al. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 2002;158(4):617-23
38. Hirota T, Kunitoku N, Sasayamal, 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
39. Pugacheva EN, Golemis EA. The focal adhesion scaffolding protein HEF1 regulates activation of the Aurora-A and Nek2 kinases at the centrosome. Nat Cell Biol 2005;7(10):937-46
40. 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
41. 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
42. Pugacheva EN, Jablonski SA, Hartman TR, et al. HEF 1-dependent Aurora A activation induces disassembly of the primary cilium. Cell 2007;129(7):1351-63
43. Vousden KH, Lu X. Live or let die: the cell's response to p53 Nat Rev Cancer 2002;2(8):594-604
44. Bode AM, Dong Z. Post-translational modification of p53 in tumorigenesis. Nat Rev Cancer 2004;4(10):793-805
45. Vousden KH. p53: death star. Cell 2000;103(5):691-4
46. Lanni JS, Jacks T. Characterization of the p53-dependent postmitotic checkpoint following spindle disruption. Mol Cell Biol 1998;18(2):1055-64
47. Katayama H, Sasai K, Kawat H, et al. Phosphorylation by Aurora kinase A induces Mdm2-mediated destabilization and inhibition of p53. Nat Genet 2004;36(1):55-62
48. 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
49. Liu Q Kaneko S, Yang L, et al. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 2004;279(50):52175-82
50. 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
51. GIET R, UZBEKOV R, CUBIZOLLES F, et al. The Xenopus laevis Aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XIEg5. J Biol Chem 1999;274(21):15005-13
52. 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
53. Conte N, Delaval B, Ginestier C, et al. TACC1-chTOG-Aurora A protein complex in breast cancer. Oncogene 2003;22(50):8102-16
54. Leroy PJ, Hunter JJ, Hoar KM, et al. Localization of human TACC3 to mitotic spindles is mediated by phosphorylation on Ser558 by Aurora A: a novel pharmacodynamic method for measuring Aurora A activity. Cancer Res 2007;67(11):5362-70
55. Toji S, Yabuta N, Hosomi T, et al. The centrosomal protein Lats2 is a phosphorylation target of Aurora-A kinase. Genes Cells 2004;9(5):383-97
56. Troiani S, Uggeri M, Moll J, et al. Searching for biomarkers of Aurora-A kinase activity: identification of in vitro substrates through a modified KESTREL approach. J Proteome Res 2005;4(4):1296-1303
57. Fuchs E, Weber K. Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem 1994;63:345-82
58. Goto H, Yasui Y, Kawajiri A, et al. Aurora-B regulates the cleavage furrow-specific vimentin phosphorylation in the cytokinetic process. J Biol Chem 2003;278(10):8526-30
59. Kawajiri A, Yasui Y, Goto H, et al. Functional significance of the specific sites phosphorylated in desmin at cleavage furrow: Aurora-B may phosphorylate and regulate type III intermediate filaments during cytokinesis coordinatedly with Rho-kinase. Mol Biol Cell 2003;14(4):1489-1500
60. Murata-Hori M, Fumoto K, Fukuta Y, et al. Myosin II regulatory light chain as a novel substrate for AIM-1, an Aurora/Ipl1p-related kinase from rat. J Biochem 2000;128(6):903-7
61. 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
62. Bishop JD, Schumacher JM. Phosphorylation of the carboxyl terminus of inner centromere protein (INCENP) by the Aurora B Kinase stimulates Aurora B kinase activity. J Biol Chem 2002;277(31):27577-80
63. Wheatley SP, Henzing AJ, Dodson H, et al. Aurora-B phosphorylation in vitro identifies a residue of survivin that is essential for its localization and binding to inner centromere protein (INCENP) in vivo. J Biol Chem 2004;279(7):5655-60
64. Gassmann R, Carvalho A, Henzing AJ, et al. Borealin: a novel chromosomal passenger required for stability of the bipolar mitotic spindle. J Cell Biol 2004;166(2):179-91
65. Andrews PD, Ovechkina Y, Morrice N, et al. Aurora B regulates MCAK at the mitotic centromere. Dev Cell 2004;6(2):253-68
66. Lan W, Zhang X, Kline-Smith SL, et al. Aurora B phosphorylates centromeric MCAK and regulates its localization and microtubule depolymerization activity. Curr Biol2004;14(4):273-86
67. Minoshima Y, Kawashima T, Hirose K, et al. Phosphorylation by Aurora B converts MgcRacGAP to a RhoGAP during cytokinesis. Dev Cell 2003;4(4):549-60
68. Yang H, Burke T, Dempsey J, et al. Mitotic requirement for Aurora A kinase is bypassed in the absence of Aurora B kinase. FEBS Len 2005;579(16):3385-91
69. Kramer G, Erdal H, Mertens HJ, et al. Differentiation between cell death modes using measurements of different soluble forms of extracellular cytokeratin 18. Cancer Res 2004;64(5):1751-6
70. Wilkinson RW, Odedra R, Heaton SP. Detection of surrogate markets of apoptosis in the peripheral blood of a preclinical tumour model treated with a selective inhibitor of Aurora B kinase (AZD1152). Eur J Cancer Suppl 2006;4(12):144
71. Wei Y, Mizzen CA, Cook RG, et al. Phosphorylation of histone H3 at serine 10 is correlated with chromosome condensation during mitosis and meiosis in tetrahymena. Proc Natl Acad Sci USA 1998;95(13):7480-4
72. Sassone-Corsi P, Mizzen CA, Cheung P, et al. Requirement of Rsk-2 for epidermal growth factor-activated phosphorylation of histone H3. Science 1999;285(5429):886-91
73. Thomson S, Clayton AL, Hazzalin CA, et al. The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase. EMBO J 1999;18(17):4779-93
74. Hendzel MJ, Wei Y, Mancini MA, et al. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma 1997;106(6):348-60
75. Crosio C, Fimia GM, Loury R, et al. Mitotic phosphorylation of histone H3: spatio-temporal regulation by mammalian Aurora kinases. Mol Cell Biol 2002;22(3):874-85
76. Hsu JY, Sun ZW, Li X, et al. Mitotic phosphorylation of histone H3 is governed by Ipl1/Aurora kinase and Glc7/PP1 phosphatase in budding yeast and nematodes. Cell 2000;102(3):279-91
77. Giet R, Glover DM. Drosophila Aurora B kinase is required for histone H3l phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokenesis. J Cell Biol 2001;152(4):669-82
78. Goto H, Yasui Y, Nigg EA, et al. Aurora-B phosphorylates histone H3 at serine28 with regard to the mitotic chromosome condensation. Genes Cells 2002;7(1):11-17
79. Choi HS, Choi BY, Cho YY, et al. Phosphorylation of histone H3 at serine 10 is indispensable for neoplastic cell transformation. Cancer Res 2005;65(13):5818-27
80. Ota T, Suto S, Katayama H, et al. Increased mitotic phosphorylation of histone H3 attributable to AIM-1/Aurora-B overexpression contributes to chromosome number instability. Cancer Res 2002;62(18):5168-77
81. Voskoglou-Nomikos T, Pater JL, Seymour L. Clinical predictive value of the in vitro cell line, human xenograft, and mouse allograft preclinical cancer models. Clin Cancer Res 2003;9(11):4227-39
82. Johnson JI, Decker S, Zaharevitz D, et al. Relationships between drug activity in NCI preclinical in vitro and in vivo models and early clinical trials. Br J Cancer 2001;84(10):1424-31
83. Simeoni M, Magni P, Cammia C, et al. Predictive pharmacokinetic-pharmacodynamic modeling of tumor growth kinetics in xenograft models after administration of anticancer agents. Cancer Res 2004;64(3):1094-101
84. Bash-Babula J, Toppmeyer D, Labassi M, et al. A Phase I/pilot study of sequential doxorubicin/vinorelbine: effects on p53 and microtubule-asaociated protein 4. Clin Cancer Res 2002;8(5):1057-64
85. Peralba JM, Degraffenried L, Friedrichs W, et al. Pharmacodynamic evaluation of CCI-779, an inhibitor of mTOR, in cancer patients. Clin Cancer Res 2003;9(8):2887-92
86. van de Vaart PJ, Belderbos J, de Jong D, et al. DNA-adduct levels as a predictor of outcome for NSCLC patients receiving daily cisplatin and radiotherapy. Int J Cancer 2000;89(2):160-6
87. Albanell J, Rojo F, Averbuch S, et al. Pharmacodynamic studies of the epidermal growth factor receptor inhibitor ZD1839 in skin from cancer patients: histopathologic and molecular consequences of receptor inhibition. J Clin Oncol 2002;20(1):110-24
88. Malik SN, Siu LL, Rowinsky EK, et al. Pharmacodynamic evaluation of the epidermal growth factor receptor inhibitor OSI-774 in human epidermis of cancer patients. Clin Cancer Res 2003;9(7):2478-86
89. Camidge DR, Davies MJ, Laud PJ, et al. Factors determining the optimal body site and method for obtaining punch biopsies of human skin ass tissue in which to assess pharmacodynamic and pharmacokinetic endpoints in drug development studies. Cancer Chemother Pharmacol 2006;57(1):52-8
90. Camidge DR, Pemberton MN, Growcott JW, et al. Assessing proliferation, cell-cycle arrest and apoptotic end points in human buccal punch biopsies for use as pharmacodynamic biomarkers in drug development. Br J Cancer 2005;93(2):208-15
91. Camidge DR, Randall KR, Foster JR, et al. Plucked human hair as a tissue in which to assess pharmacodynamic end points during drug development studies. Br J Cancer 2005;92(10):1837-41