The ongoing roll-out of Aurora kinase inhibitors in cancer treatment

Drugs of the Future

Volumn 35, Issue 10, 2010, Pages 845-858

  Dotan, E ^a   Cohen, Roger B ^b  

^a FOX CHASE CANCER CENTER   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 CYCLOPROPYL 3 [3 (5 MORPHOLINOMETHYL 1H BENZIMIDAZOL 2 YL) 1H PYRAZOL 4 YL]UREA; 4 [[9 CHLORO 7 (2,6 DIFLUOROPHENYL) 5H PYRIMIDO[5,4 D][2]BENZAZEPIN 2 YL]AMINO]BENZOIC ACID; ALISERTIB; AMG 900; AURORA A KINASE; AURORA B KINASE; AURORA C KINASE; AURORA KINASE INHIBITOR; BARASERTIB; BEVACIZUMAB; BI 811283; CCT 129202; CYC 116; CYTARABINE; DANUSERTIB; DAUNORUBICIN; DOCETAXEL; GSK 1070916; IRINOTECAN; JNJ 7706621; N [4 [6 METHOXY 7 (3 MORPHOLINOPROPOXY) 4 QUINAZOLINYLAMINO]PHENYL]BENZAMIDE; PACLITAXEL; PF 03814735; PHA 680632; RECOMBINANT GRANULOCYTE COLONY STIMULATING FACTOR; SNS 314; TAXANE DERIVATIVE; TOZASERTIB; UNCLASSIFIED DRUG; VINCRISTINE; VORINOSTAT;

ACUTE GRANULOCYTIC LEUKEMIA; ADVANCED CANCER; ANEUPLOIDY; APOPTOSIS; CANCER CELL; CANCER CELL CULTURE; CANCER CHEMOTHERAPY; CANCER INHIBITION; CANCER SURVIVAL; CARCINOGENESIS; CELL CYCLE REGULATION; CELL DEATH; CELL DIVISION; CELL GROWTH; CELL MATURATION; CHROMOSOME CONDENSATION; CHRONIC MYELOID LEUKEMIA; COLORECTAL CANCER; CONTINUOUS INFUSION; CYTOKINESIS; DIARRHEA; DRUG POTENTIATION; DRUG TOLERABILITY; ENZYME ACTIVATION; ENZYME INACTIVATION; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL SYMPTOM; GASTROINTESTINAL TOXICITY; GENOMIC INSTABILITY; HEMATOLOGIC MALIGNANCY; HERPES ZOSTER; HUMAN; LIPOSARCOMA; METASTASIS; MITOSIS INHIBITION; MUCOSA INFLAMMATION; MULTIPLE CYCLE TREATMENT; NAUSEA; NEUTROPENIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROSTATE CANCER; PROTEIN FUNCTION; RECOMMENDED DRUG DOSE; REVIEW; SENESCENCE; SOLID TUMOR; SOMNOLENCE; STOMATITIS; THROMBOCYTOPENIA; TREATMENT RESPONSE; VOMITING;

EID: 79956188438     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2010.035.010.1529819     Document Type: Review

References (150)

1. Fu, J., Bian, M., Jiang, Q., Zhang, C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res 2007, 5(1): 1-10.
2. Vader, G., Lens, S.M. The Aurora kinase family in cell division and cancer. Biochim Biophys Acta 2008, 1786(1): 60-72.
3. Glover, D.M., Leibowitz, M.H., McLean, D.A., Parry, H. Mutations in aurora prevent centrosome separation leading to the formation of monopolar spindles. Cell 1995, 81(1): 95-105.
4. Eyers, P.A., Maller, J.L. Regulation of Xenopus Aurora A activation by TPX2. J Biol Chem 2004, 279(10): 9008-15. (Pubitemid 38295963)
5. Sessa, F., Mapelli, M., Ciferri, C. et al. Mechanism of Aurora B activation by INCENP and inhibition by hesperadin. Mol Cell 2005, 18(3): 379-91. (Pubitemid 41350542)
6. 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. (Pubitemid 37352779)
7. Cheetham, G.M., Knegtel, R.M., Coll, J.T. et al. Crystal structure of aurora-2, an oncogenic serine/threonine kinase. J Biol Chem 2002, 277(45): 42419-22. (Pubitemid 35285606)
8. Marumoto, T., Honda, S., Hara, T., Nitta, M., Hirota, T., Kohmura, E., Saya, H. Aurora-A kinase maintains the fidelity of early and late mitotic events in HeLa cells. J Biol Chem 2003, 278(51): 51786-95. (Pubitemid 38020425)
9. Berdnik, D., Knoblich, J.A. Drosophila Aurora-A is required for centrosome maturation and actin-dependent asymmetric protein localization during mitosis. Curr Biol 2002, 12(8): 640-7. (Pubitemid 34315847)
10. 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. (Pubitemid 37159255)
11. Dutertre, S., Cazales, M., Quaranta, M. et al. Phosphorylation of CDC25B by Aurora-A at the centrosome contributes to the G2-M transition. J Cell Sci 2004, 117(Pt 12): 2523-31. (Pubitemid 38877848)
12. Carvajal, R.D., Tse, A., Schwartz, G.K. Aurora kinases: New targets for cancer therapy. Clin Cancer Res 2006, 12(23): 6869-75. (Pubitemid 44974478)
13. Dutertre, S., Descamps, S., Prigent, C. On the role of aurora-A in centrosome function. Oncogene 2002, 21(40): 6175-83.
14. Carmena, M., Ruchaud, S., Earnshaw, W.C. Making the Auroras glow: Regulation of Aurora A and B kinase function by interacting proteins. Curr Opin Cell Biol 2009, 21(6): 796-805.
15. Wittmann, T., Wilm, M., Karsenti, E., Vernos, I. TPX2, a novel Xenopus MAP involved in spindle pole organization. J Cell Biol 2000, 149(7): 1405-18. (Pubitemid 30437615)
16. Eyers, P.A., Erikson, E., Chen, L.G., Maller, J.L. A novel mechanism for activation of the protein kinase Aurora A. Curr Biol 2003, 13(8): 691-7. (Pubitemid 36453320)
17. Dar, A.A., Goff, L.W., Majid, S., Berlin, J., El-Rifai, W. Aurora kinase inhibitors - Rising stars in cancer therapeutics? Mol Cancer Ther 2010, 9(2): 268-78.
18. Swedlow, J.R., Hirano, T. The making of the mitotic chromosome: Modern insights into classical questions. Mol Cell 2003, 11(3): 557-69. (Pubitemid 36385113)
19. Giet, R., Glover, D.M. Drosophila aurora B kinase is required for histone H3 phosphorylation and condensin recruitment during chromosome condensation and to organize the central spindle during cytokinesis. J Cell Biol 2001, 152(4): 669-82.
20. Honda, R., Korner, R., Nigg, E.A. Exploring the functional interactions between Aurora B, INCENP, and survivin in mitosis. Mol Biol Cell 2003, 14(8): 3325-41.
21. Murata-Hori, M., Wang, Y.L. The kinase activity of aurora B is required for kinetochore-microtubule interactions during mitosis. Curr Biol 2002, 12(11): 894-9. (Pubitemid 34689223)
22. Severson, A.F., Hamill, D.R., Carter, J.C., Schumacher, J., Bowerman, B. The aurora-related kinase AIR-2 recruits ZEN-4/CeMKLP1 to the mitotic spindle at metaphase and is required for cytokinesis. Curr Biol 2000, 10(19): 1162-71.
23. Guse, A., Mishima, M., Glotzer, M. Phosphorylation of ZEN-4/MKLP1 by aurora B regulates completion of cytokinesis. Curr Biol 2005, 15(8): 778-86. (Pubitemid 40599935)
24. 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. (Pubitemid 36437561)
25. Buvelot, S., Tatsutani, S.Y., Vermaak, D., Biggins, S. The budding yeast Ipl1/Aurora protein kinase regulates mitotic spindle disassembly. J Cell Biol 2003, 160(3): 329-39. (Pubitemid 36182724)
26. Bernard, M., Sanseau, P., Henry, C., Couturier, A., Prigent, C. Cloning of STK13, a third human protein kinase related to Drosophila aurora and bud-ding yeast Ipl1 that maps on chromosome 19q13.3-ter. Genomics 1998, 53(3): 406-9. (Pubitemid 28527647)
27. Tseng, T.C., Chen, S.H., Hsu, Y.P., Tang, T.K. Protein kinase profile of sperm and eggs: cloning and characterization of two novel testis-specific protein kinases (AIE1, AIE2) related to yeast and fly chromosome segregation regulators. DNA Cell Biol 1998, 17(10): 823-33.
28. Kimura, M., Matsuda, Y., Yoshioka, T., Okano, Y. Cell cycle-dependent expression and centrosome localization of a third human aurora/Ipl1-related protein kinase, AIK3. J Biol Chem 1999, 274(11): 7334-40.
29. Yan, X., Cao, L., Li, Q. et al. Aurora C is directly associated with survivin and required for cytokinesis. Genes Cells 2005, 10(6): 617-26. (Pubitemid 40867492)
30. Li, X., Sakashita, G., Matsuzaki, H. et al. Direct association with inner centromere protein (INCENP) activates the novel chromosomal passenger protein, Aurora-C. J Biol Chem 2004, 279(45): 47201-11. (Pubitemid 39518377)
31. Sasai, K., Katayama, H., Stenoien, D.L. 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. (Pubitemid 40012993)
32. Kimmins, S., Crosio, C., Kotaja, N. et al. Differential functions of the Aurora-B and Aurora-C kinases in mammalian spermatogenesis. Mol Endocrinol 2007, 21(3): 726-39.
33. Dieterich, K., Soto Rifo, R., Faure, A.K. et al. Homozygous mutation of AURKC yields large-headed polyploid spermatozoa and causes male infertility. Nat Genet 2007, 39(5): 661-5. (Pubitemid 46676111)
34. Meraldi, P., Honda, R., Nigg, E.A. Aurora-A overexpression reveals tetraploidization as a major route to centrosome amplification in p53-/- cells. EMBO J 2002, 21(4): 483-92. (Pubitemid 34174030)
35. Bischoff, J.R., 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. (Pubitemid 28254378)
36. Littlepage, L.E., Wu, H., Andresson, T., Deanehan, J.K., Amundadottir, L.T., Ruderman, J.V. Identification of phosphorylated residues that affect the activity of the mitotic kinase Aurora-A. Proc Natl Acad Sci U S A 2002, 99(24): 15440-5. (Pubitemid 35403953)
37. Nadler, Y., Camp, R.L., Schwartz, C., Rimm, D.L., Kluger, H.M., Kluger, Y. Expression of Aurora A (but not Aurora B) is predictive of survival in breast cancer. Clin Cancer Res 2008, 14(14): 4455-62.
38. Kulkarni, A.A., Loddo, M., Leo, E. et al. DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma. Clin Cancer Res 2007, 13(20): 6153-61. (Pubitemid 350075075)
39. Mendiola, M., Barriuso, J., Marino-Enriquez, A. et al. Aurora kinases as prognostic biomarkers in ovarian carcinoma. Hum Pathol 2009, 40(5): 631-8.
40. Smith, S.L., Bowers, N.L., Betticher, D.C. et al. Overexpression of aurora B kinase (AURKB) in primary non-small cell lung carcinoma is frequent, generally driven from one allele, and correlates with the level of genetic instability. Br J Cancer 2005, 93(6): 719-29. (Pubitemid 41486464)
41. Baba, Y., Nosho, K., Shima, K. et al. Aurora-A expression is independently associated with chromosomal instability in colorectal cancer. Neoplasia 2009, 11(5): 418-25.
42. Chieffi, P., Cozzolino, L., Kisslinger, A. et al. Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate 2006, 66(3): 326-33. (Pubitemid 43191232)
43. Shang, X., Burlingame, S.M., Okcu, M.F. 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.
44. Wang, X., Zhou, Y.X., Qiao, W., Tominaga, Y., Ouchi, M., Ouchi, T., Deng, C.X. Overexpression of aurora kinase A in mouse mammary epithelium induces genetic instability preceding mammary tumor formation. Oncogene 2006, 25(54): 7148-58. (Pubitemid 44764184)
45. Kanda, A., Kawai, H., Suto, S., Kitajima, S., Sato, S., Takata, T., Tatsuka, M. Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation. Oncogene 2005, 24(49): 7266-72. (Pubitemid 41622230)
46. den Hollander, J., Rimpi, S., Doherty, J.R. 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.
47. Liu, Q., Kaneko, S., Yang, L., Feldman, R.I., Nicosia, S.V., Chen, J., Cheng, J.Q. Aurora-A abrogation of p53 DNA binding and transactivation activity by phosphorylation of serine 215. J Biol Chem 2004, 279(50): 52175-82. (Pubitemid 39656591)
48. Chen, S.S., Chang, P.C., Cheng, Y.W., Tang, F.M., Lin, Y.S. Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function. EMBO J 2002, 21(17): 4491-9.
49. 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. (Pubitemid 38056208)
50. Dar, A.A., Belkhiri, A., Ecsedy, J., Zaika, A., El-Rifai, W. Aurora kinase A inhibition leads to p73-dependent apoptosis in p53-deficient cancer cells. Cancer Res 2008, 68(21): 8998-9004.
51. Ouchi, M., Fujiuchi, N., Sasai, K. et al. BRCA1 phosphorylation by Aurora-A in the regulation of G2 to M transition. J Biol Chem 2004, 279(19): 19643-8. (Pubitemid 38623401)
52. Taga, M., Hirooka, E., Ouchi, T. Essential roles of mTOR/Akt pathway in Aurora-A cell transformation. Int J Biol Sci 2009, 5(5): 444-50.
53. Astsaturov, I., Ratushny, V., Sukhanova, A. et al. Synthetic lethal screen of an EGFR-centered network to improve targeted therapies. Sci Signal 2010, 3(140): ra67.
54. 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. (Pubitemid 35024587)
55. Gascoigne, K.E., Taylor, S.S. How do anti-mitotic drugs kill cancer cells? J Cell Sci 2009, 122(Pt 15): 2579-85.
56. Jordan, M.A., Wendell, K., Gardiner, S., Derry, W.B., Copp, H., Wilson, L. Mitotic block induced in HeLa cells by low concentrations of paclitaxel (Taxol) results in abnormal mitotic exit and apoptotic cell death. Cancer Res 1996, 56(4): 816-25. (Pubitemid 26055472)
57. Chen, J.G., Horwitz, S.B. Differential mitotic responses to microtubule-stabilizing and -destabilizing drugs. Cancer Res 2002, 62(7): 1935-8. (Pubitemid 34408432)
58. Sasai, K., Parant, J.M., Brandt, M.E. et al. Targeted disruption of Aurora A causes abnormal mitotic spindle assembly, chromosome misalignment and embryonic lethality. Oncogene 2008, 27(29): 4122-7. (Pubitemid 351931992)
59. Hoar, K., Chakravarty, A., Rabino, C., Wysong, D., Bowman, D., Roy, N., Ecsedy, J.A. 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. (Pubitemid 46906573)
60. Hata, T., Furukawa, T., Sunamura, M. et al. RNA interference targeting aurora kinase a suppresses tumor growth and enhances the taxane chemosensitivity in human pancreatic cancer cells. Cancer Res 2005, 65(7): 2899-905. (Pubitemid 40490094)
61. Gully, C.P., Zhang, F., Chen, J. et al. Antineoplastic effects of an Aurora B kinase inhibitor in breast cancer. Mol Cancer 2010, 9: 42.
62. Addepalli, M.K., Ray, K.B., Kumar, B., Ramnath, R.L., Chile, S., Rao, H. RNAi-mediated knockdown of AURKB and EGFR shows enhanced therapeutic efficacy in prostate tumor regression. Gene Ther 2010, 17(3): 352-9.
63. Cha, T.L., Chuang, M.J., Wu, S.T. et al. Dual degradation of aurora A and B kinases by the histone deacetylase inhibitor LBH589 induces G2-M arrest and apoptosis of renal cancer cells. Clin Cancer Res 2009, 15(3): 840-50.
64. Scharer, C.D., Laycock, N., Osunkoya, A.O., Logani, S., McDonald, J.F., Benigno, B.B., Moreno, C.S. Aurora kinase inhibitors synergize with paclitaxel to induce apoptosis in ovarian cancer cells. J Transl Med 2008, 6: 79.
65. Lin, Y.G., Immaneni, A., Merritt, W.M. et al. Targeting aurora kinase with MK-0457 inhibits ovarian cancer growth. Clin Cancer Res 2008, 14(17): 5437-46.
66. Cheetham, G.M., Charlton, P.A., Golec, J.M., Pollard, J.R. Structural basis for potent inhibition of the Aurora kinases and a T315I multi-drug resistant mutant form of Abl kinase by VX-680. Cancer Lett 2007, 251(2): 323-9. (Pubitemid 46669805)
67. Evans, R., Naber, C., Steffler, T. et al. Aurora A kinase RNAi and small molecule inhibition of Aurora kinases with VE-465 induce apoptotic death in multiple myeloma cells. Leuk Lymphoma 2008, 49(3): 559-69. (Pubitemid 351298342)
68. Barton, V.N., Foreman, N.K., Donson, A.M., Birks, D.K., Handler, M.H., Vibhakar, R. Aurora kinase A as a rational target for therapy in glioblastoma. J Neurosurg Pediatr 2010, 6(1): 98-105.
69. El-Sheikh, A., Fan, R., Birks, D., Donson, A., Foreman, N.K., Vibhakar, R. Inhibition of Aurora Kinase A enhances chemosensitivity of medulloblastoma cell lines. Pediatr Blood Cancer 2010, 55(1): 35-41.
70. 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. (Pubitemid 36800605)
71. Hauf, S., Cole, R.W., 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. (Pubitemid 36529847)
72. Kallio, M.J., McCleland, M.L., Stukenberg, P.T., Gorbsky, G.J. Inhibition of aurora B kinase blocks chromosome segregation, overrides the spindle checkpoint, and perturbs microtubule dynamics in mitosis. Curr Biol 2002, 12(11): 900-5. (Pubitemid 34689224)
73. Ditchfield, C., Johnson, V.L., 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. (Pubitemid 36529846)
74. Traynor, A.M., 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 2010, Epub ahead of print.
75. Soncini, C., Carpinelli, P., Gianellini, L. et al. PHA-680632, a novel Aurora kinase inhibitor with potent antitumoral activity. Clin Cancer Res 2006, 12(13): 4080-9. (Pubitemid 44078096)
76. Carpinelli, P., Ceruti, R., Giorgini, M.L. et al. PHA-739358, a potent inhibitor of Aurora kinases with a selective target inhibition profile relevant to cancer. Mol Cancer Ther 2007, 6(12, Pt. 1): 3158-68.
77. Gontarewicz, A., Balabanov, S., Keller, G. et al. Simultaneous targeting of Aurora kinases and Bcr-Abl kinase by the small molecule inhibitor PHA- 739358 is effective against imatinib-resistant BCR-ABL mutations including T315I. Blood 2008, 111(8): 4355-64.
78. Steeghs, N., Eskens, F.A., Gelderblom, H. et al. Phase I pharmacokinetic and pharmacodynamic study of the aurora kinase inhibitor danusertib in patients with advanced or metastatic solid tumors. J Clin Oncol 2009, 27(30): 5094-101.
79. Cohen, R.B., Jones, S.F., Aggarwal, C. et al. A phase I dose-escalation study of danusertib (PHA-739358) administered as a 24-hour infusion with and without granulocyte colony-stimulating factor in a 14-day cycle in patients with advanced solid tumors. Clin Cancer Res 2009, 15(21): 6694-701.
80. th Annu Meet Am Soc Clin Oncol (ASCO) (June 4-8, Chicago) 2010] 2010, 28(15, Suppl.): Abst 5014.
81. th Annu Meet Am Soc Clin Oncol (ASCO) (June 4-8, Chicago) 2010] 2010, 28(15, Suppl.): Abst e13558.
82. Rosen, P.J., Tolcher, A.W., Lee, P. et al. Phase I study of danusertib (D) in combination with bevacizumab (B) in solid tumors. J Clin Oncol [46th Annu Meet Am Soc Clin Oncol (ASCO) (June 4-8, Chicago) 2010] 2010, 28(15, Suppl.): Abst 3066.
83. st Annu Meet Am Soc Hematol (Dec 5-8, New Orleans) 2009] 2009, 114(22): Abst 864.
84. Wilkinson, R.W., Odedra, R., Heaton, S.P. 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. (Pubitemid 46955132)
85. Walsby, E., Walsh, V., Pepper, C., Burnett, A., Mills, K. Effects of the aurora kinase inhibitors AZD1152-HQPA and ZM447439 on growth arrest and polyploidy in acute myeloid leukemia cell lines and primary blasts. Haematologica 2008, 93(5): 662-9. (Pubitemid 351669305)
86. Evans, R.P., Naber, C., Steffler, T. et al. The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma. Br J Haematol 2008, 140(3): 295-302.
87. Berlin, J., Posey, J., Tchekmedyian, S. et al. Panitumumab with irinotecan/ leucovorin/5-fluorouracil for first-line treatment of metastatic colorectal cancer. Clin Colorectal Cancer 2007, 6(6): 427-32. (Pubitemid 46658516)
88. Nair, J.S., de Stanchina, E., Schwartz, G.K. The topoisomerase I poison CPT-11 enhances the effect of the aurora B kinase inhibitor AZD1152 both in vitro and in vivo. Clin Cancer Res 2009, 15(6): 2022-30.
89. Schellens, J.H., Boss, D., Witteveen, P.O. et al. Phase I and pharmacological study of the novel aurora kinase inhibitor AZD1152 J Clin Oncol [42nd Annu Meet Am Soc Clin Oncol (ASCO) (June 3-6, Atlanta) 2006] 2006, 24(18, Suppl.): Abst 3008.
90. st Annu Meet Am Soc Hematol (Dec 5-8, New Orleans) 2009] 2009, 114(22): Abst 2080.
91. Long, Z.J., Xu, J., Yan, M. et al. ZM 447439 inhibition of aurora kinase induces Hep2 cancer cell apoptosis in three-dimensional culture. Cell Cycle 2008, 7(10): 1473-9. (Pubitemid 351872587)
92. Gadea, B.B., Ruderman, J.V. Aurora kinase inhibitor ZM447439 blocks chromosome-induced spindle assembly, the completion of chromosome condensation, and the establishment of the spindle integrity checkpoint in Xenopus egg extracts. Mol Biol Cell 2005, 16(3): 1305-18. (Pubitemid 40349566)
93. Li, M., Jung, A., Ganswindt, U. et al. Aurora kinase inhibitor ZM447439 induces apoptosis via mitochondrial pathways. Biochem Pharmacol 2010, 79(2): 122-9.
94. Manfredi, M.G., Ecsedy, J.A., Meetze, K.A. et al. Antitumor activity of MLN8054, an orally active small-molecule inhibitor of Aurora A kinase. Proc Natl Acad Sci U S A 2007, 104(10): 4106-11. (Pubitemid 47181586)
95. Huck, J.J., 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.
96. Mahadevan, D., Qi, W., Cooke, L., Lui, X., Persky, D.O., Rimsza, L.M., Miller, T.P. Targeting Aurora kinase in aggressive B-cell non-Hodgkin's lymphomas. Blood [51st Annu Meet Am Soc Hematol (Dec 5-8, New Orleans) 2009] 2009, 114(22): Abst 284.
97. 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.
98. Dees, E.C., Infante, J.R., Burris, H.A. et al. Phase I study of the investigational drug MLN8237, an Aurora A kinase (AAK) inhibitor, in patients (pts) with solid tumors. J Clin Oncol [46th Annu Meet Am Soc Clin Oncol (ASCO) (June 4-8, Chicago) 2010] 2010, 28(15, Suppl.): Abst 3010.
99. th Annu Meet Am Soc Clin Oncol (ASCO) (May 29-June 2, Orlando) 2009] 2009, 27(15, Suppl.): Abst 2565.
100. Emanuel, S., Rugg, C.A., Gruninger, R.H. et al. The in vitro and in vivo effects of JNJ-7706621: a dual inhibitor of cyclin-dependent kinases and aurora kinases. Cancer Res 2005, 65(19): 9038-46. (Pubitemid 41377396)
101. Danhier, F., Ucakar, B., Magotteaux, N., Brewster, M.E., Preat, V. Active and passive tumor targeting of a novel poorly soluble cyclin dependent kinase inhibitor, JNJ-7706621. Int J Pharm 2010, 392(1-2): 20-8.
102. Jani, J.P., Arcari, J., Bernardo, V. et al. PF-03814735, an orally bioavailable small molecule aurora kinase inhibitor for cancer therapy. Mol Cancer Ther 2010, 9(4): 883-94.
103. th Annu Meet Am Soc Clin Oncol (ASCO) (May 30-June 3, Chicago) 2008] 2008, 26(15, Suppl.): Abst 2517.
104. Sloane, D.A., Trikic, M.Z., Chu, M.L. et al. Drug-resistant aurora A mutants for cellular target validation of the small molecule kinase inhibitors MLN8054 and MLN8237. ACS Chem Biol 2010, 5(6): 563-76.
105. Chung, G., Kendall, R., Geuns-Meyer, S., Payton, M. In vitro characterization of AMG 900, an orally active small molecule inhibitor of aurora kinases in phase 1 clinical trials. Mol Cancer Ther [AACR-NCI-EORTC Int Conf Mol Targets Cancer Ther (Nov 15-19, Boston) 2009] 2009, 8(12, Suppl.): Abst A261.
106. Gautschi, O., Heighway, J., Mack, P.C., Purnell, P.R., Lara, P.N., Jr., Gandara, D.R. Aurora kinases as anticancer drug targets. Clin Cancer Res 2008, 14(6): 1639-48. (Pubitemid 351471713)
107. Lee, E.C., Frolov, A., Li, R., Ayala, G., Greenberg, N.M. Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res 2006, 66(10): 4996-5002. (Pubitemid 43844918)
108. Milross, C.G., Mason, K.A., Hunter, N.R., Chung, W.K., Peters, L.J., Milas, L. Relationship of mitotic arrest and apoptosis to antitumor effect of paclitaxel. J Natl Cancer Inst 1996, 88(18): 1308-14. (Pubitemid 26301619)
109. Schimming, R., Mason, K.A., Hunter, N., Weil, M., Kishi, K., Milas, L. Lack of correlation between mitotic arrest or apoptosis and antitumor effect of docetaxel. Cancer Chemother Pharmacol 1999, 43(2): 165-72. (Pubitemid 29045036)
110. Macurek, 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.
111. Mori, D., Yano, Y., Toyo-oka, K. et al. NDEL1 phosphorylation by Aurora-A kinase is essential for centrosomal maturation, separation, and TACC3 recruitment. Mol Cell Biol 2007, 27(1): 352-67. (Pubitemid 46013256)
112. Abe, Y., Ohsugi, M., Haraguchi, K., Fujimoto, J., Yamamoto, T. LATS2-Ajuba complex regulates gamma-tubulin recruitment to centrosomes and spindle organization during mitosis. FEBS Lett 2006, 580(3): 782-8. (Pubitemid 43152297)
113. 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. (Pubitemid 38771930)
114. Hannak, E., Kirkham, M., Hyman, A.A., Oegema, K. Aurora-A kinase is required for centrosome maturation in Caenorhabditis elegans. J Cell Biol 2001, 155(7): 1109-16.
115. Zhao, Z.S., Lim, J.P., Ng, Y.W., Lim, L., Manser, E. The GIT-associated kinase PAK targets to the centrosome and regulates Aurora-A. Mol Cell 2005, 20(2): 237-49. (Pubitemid 41484169)
116. Kufer, T.A., Sillje, H.H., Korner, R., Gruss, O.J., Meraldi, P., Nigg, E.A. Human TPX2 is required for targeting Aurora-A kinase to the spindle. J Cell Biol 2002, 158(4): 617-23. (Pubitemid 34920101)
117. Tsai, M.Y., 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. (Pubitemid 36322252)
118. Giet, R., Uzbekov, R., Cubizolles, F., Le Guellec, K., Prigent, C. The Xenopus laevis aurora-related protein kinase pEg2 associates with and phosphorylates the kinesin-related protein XlEg5. J Biol Chem 1999, 274(21): 15005-13.
119. Bishop, J.D., Schumacher, J.M. 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. (Pubitemid 34966697)
120. Yue, Z., Carvalho, A., Xu, Z. et al. Deconstructing Survivin: comprehensive genetic analysis of survivin function by conditional knockout in a vertebrate cell line. J Cell Biol 2008, 183(2): 279-96.
121. Bolton, M.A., Lan, W., Powers, S.E., McCleland, M.L., Kuang, J., Stukenberg, P.T. Aurora B kinase exists in a complex with survivin and INCENP and its kinase activity is stimulated by survivin binding and phosphorylation. Mol Biol Cell 2002, 13(9): 3064-77. (Pubitemid 35034246)
122. Kelly, A.E., Sampath, S.C., Maniar, T.A., Woo, E.M., Chait, B.T., Funabiki, H. Chromosomal enrichment and activation of the aurora B pathway are coupled to spatially regulate spindle assembly. Dev Cell 2007, 12(1): 31-43. (Pubitemid 46002596)
123. Han, Z., Riefler, G.M., Saam, J.R., Mango, S.E., Schumacher, J.M. The C. elegans Tousled-like kinase contributes to chromosome segregation as a substrate and regulator of the Aurora B kinase. Curr Biol 2005, 15(10): 894-904. (Pubitemid 40772059)
124. Zachos, G., Black, E.J., Walker, M., Scott, M.T., Vagnarelli, P., Earnshaw, W.C., Gillespie, D.A. Chk1 is required for spindle checkpoint function. Dev Cell 2007, 12(2): 247-60. (Pubitemid 46193970)
125. Sugiyama, K., Sugiura, K., Hara, T. et al. Aurora-B associated protein phosphatases as negative regulators of kinase activation. Oncogene 2002, 21(20): 3103-11. (Pubitemid 34548081)
126. Sun, L., Gao, J., Dong, X. et al. EB1 promotes Aurora-B kinase activity through blocking its inactivation by protein phosphatase 2A. Proc Natl Acad Sci U S A 2008, 105(20): 7153-8. (Pubitemid 351754447)
127. Lampson, M.A., Kapoor, T.M. The human mitotic checkpoint protein BubR1 regulates chromosome-spindle attachments. Nat Cell Biol 2005, 7(1): 93-8. (Pubitemid 40123388)
128. Morrow, C.J., Tighe, A., Johnson, V.L., Scott, M.I., Ditchfield, C., Taylor, S.S. Bub1 and aurora B cooperate to maintain BubR1-mediated inhibition of APC/CCdc20. J Cell Sci 2005, 118(Pt. 16): 3639-52.
129. Tanaka, T., Kimura, M., Matsunaga, K., Fukada, D., Mori, H., Okano, Y. Centrosomal kinase AIK1 is overexpressed in invasive ductal carcinoma of the breast. Cancer Res 1999, 59(9): 2041-4. (Pubitemid 29217660)
130. Nishida, N., Nagasaka, T., Kashiwagi, K., Boland, C.R., Goel, A. High copy amplification of the Aurora-A gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther 2007, 6(4): 525-33. (Pubitemid 47328326)
131. Sen, S., Zhou, H., Zhang, R.D. et al. Amplification/overexpression of a mitotic kinase gene in human bladder cancer. J Natl Cancer Inst 2002, 94(17): 1320-9.
132. 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. (Pubitemid 32275658)
133. Rojanala, S., Han, H., Munoz, R.M., Browne, W., Nagle, R., Von Hoff, D.D., Bearss, D.J. The mitotic serine threonine kinase, Aurora-2, is a potential target for drug development in human pancreatic cancer. Mol Cancer Ther 2004, 3(4): 451-7. (Pubitemid 39193722)
134. Landen, C.N., Jr., Lin, Y.G., 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. (Pubitemid 47105971)
135. Xu, H.T., Ma, L., Qi, F.J. 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. (Pubitemid 43886801)
136. Zhang, X.H., Rao, M., Loprieato, J.A. et al. Aurora A, Aurora B and survivin are novel targets of transcriptional regulation by histone deacetylase inhibitors in non-small cell lung cancer. Cancer Biol Ther 2008, 7(9): 1388-97.
137. 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 2003, 10(5): 1275-9.
138. Sorrentino, R., Libertini, S., Pallante, P.L. et al. Aurora B overexpression associates with the thyroid carcinoma undifferentiated phenotype and is required for thyroid carcinoma cell proliferation. J Clin Endocrinol Metab 2005, 90(2): 928-35. (Pubitemid 40279218)
139. Zeng, W.F., Navaratne, K., Prayson, R.A., Weil, R.J. Aurora B expression correlates with aggressive behaviour in glioblastoma multiforme. J Clin Pathol 2007, 60(2): 218-21.
140. th Annu Meet Am Soc Clin Oncol (ASCO) (May 29-June 2, Orlando) 2009] 2009, 27(15, Suppl.): Abst 2536.
141. Arbitrario, J.P., Belmont, B.J., Evanchik, M.J. et al. SNS-314, a pan-Aurora kinase inhibitor, shows potent anti-tumor activity and dosing
142. th Annu Meet Am Soc Clin Oncol (ASCO) (June 4-8, Chicago) 2010] 2010, 28(15, Suppl.): Abst 3011.
143. Hardwicke, M.A., Oleykowski, C.A., Plant, R. et al. GSK1070916, a potent Aurora B/C kinase inhibitor with broad antitumor activity in tissue culture cells and human tumor xenograft models. Mol Cancer Ther 2009, 8(7): 1808-17.
144. Adams, N.D., Adams, J.L., Burgess, J.L. et al. Discovery of GSK1070916, a potent and selective inhibitor of Aurora B/C kinase. J Med Chem 2010, 53(10): 3973-4001.
145. Dawson, M.A., Curry, J.E., Barber, K. et al. AT9283, a potent inhibitor of the Aurora kinases and Jak2, has therapeutic potential in myeloproliferative disorders. Br J Haematol 2010, 150(1): 46-57.
146. Kristeleit, R., Calvert, H., Arkenau, H. et al. A phase I study of AT9283, an aurora kinase inhibitor, in patients with refractory solid tumors. J Clin Oncol [45th Annu Meet Am Soc Clin Oncol (ASCO) (May 29-June 2, Orlando) 2009] 2009, 27(15, Suppl.): Abst 2566.
147. Howard, S., Berdini, V., Boulstridge, J.A. et al. Fragment-based discovery of the pyrazol-4-yl urea (AT9283), a multitargeted kinase inhibitor with potent aurora kinase activity. J Med Chem 2009, 52(2): 379-88.
148. Tanaka, R., Squires, M.S., Kimura, S. et al. Activity of the multi-targeted kinase inhibitor, AT9283, in imatinib-resistant BCR-ABL positive leukemic cells. Blood 2010, 116(12):2089-95.
149. Griffiths, G., Scaerou, F., Midgley, C. et al. Anti-tumor activity of CYC116, a novel small molecule inhibitor of Aurora kinases and VEGFR2. Proc Am Assoc Cancer Res (AACR) 2008, 49: Abst 5644.
150. Chan, F., Sun, C., Perumal, M. et al. Mechanism of action of the Aurora kinase inhibitor CCT129202 and in vivo quantification of biological activity. Mol Cancer Ther 2007, 6(12, Pt. 1): 3147-57.