MGCD0103 Mocetinostat ul biomarker of sensitivity for B cell lymphoma

ul biomarker of sensitivity for B cell lymphoma inhibition of the chromosomal passenger protein complex. Therefore, incorporation of a pan aurora kinase inhibitor into standard MGCD0103 Mocetinostat R CHOP or some components should be evaluated in phase II studies of c Myc driven aggressive B and T cell lymphomas. The major side effects of aurora kinase inhibition are neutropenia, mucositis and alopecia which appear to mimick traditional chemotherapy agents. Therefore, dosing and scheduling without compromising efficacy are key to successful anti cancer therapy. Agents that exquisitely synergize with aurora kinase inhibition without any additional adverse events are likely to move forward as effective therapies for many human malignancies. Acknowledgments We wish to thank Annette Krzysik for preparing Figure 1 Annotated Bibliography 1.
World cancer report. 2008 . online/wcr/2008/wcr_2008.pdf 2. The global economic cost of cancer. . cancer/acs/groups/content/internationalaffairs/documents/document/ acspc 026203.pdf 3. Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol. 2003, 4:842 54. 4. Ducat PHA-739358 D, Zheng Y. Aurora kinases in spindle assembly and chromosome segregation. Exp Cell Res. 2004, 301:60 7. 5. Marumoto T, Zhang D, Saya H. Aurora A, a guardian of poles. Nat Rev Cancer. 2005, 5:42 50. 6. Fu J, Bian M, Jiang Q, Zhang C. Roles of Aurora kinases in mitosis and tumorigenesis. Mol Cancer Res. 2007, 5:1 10. 7�? Kobayashi M, Nakamura S, Ono T, et al. Analysis of aurora kinase expressions and cell cycle regulation by aurora C in leukemia cells.
Blood . 2006, 108 abstr 1366. Implicates overexpression of aurora C kinase in human leukemia, rather than restricted to testicular meiosis. 8. Slattery SD, Mancini MA, Brinkley BR, Hall RM. Aurora C kinase supports mitotic progression in the absence of aurora B. Cell Cycle. 2009, 8:2986 97. 9. Zhang X. Aurora kinases. Curr Biol. 2008, 18:R146 8. 10. Carvajal RD, Tse A, Schwartz GK. Aurora kinases: new targets for cancer therapy. Clin Cancer Res. 2006, 12:6869 75. 11. Girdler F, Gascoigne KE, Eyers PA, et al. Validating aurora B as an anti cancer drug target. J Cell Sci. 2006, 119:3664 75. 12. Nishida N, Nagasaka T, Kashiwagi K, et al. High copy amplification of the aurora A gene is associated with chromosomal instability phenotype in human colorectal cancers. Cancer Biol Ther.
2007, 6:525 33. 13. 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, 9:1420 6. 14. Anand S, Penrhyn Lowe S, Venkitaraman AR. Aurora A amplification overrides the mitotic spindle assembly checkpoint, inducing resistance to Taxol. Cancer Cell. 2003, 3:51 62. Green et al. Page 14 Expert Opin Drug Discov. Author manuscript, available in PMC 2012 March 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript 15•�? Karthigeyan D, Prasad SB, Shandilya J, et al. Biology of aurora A kinase: implications in cancer manifestation and therapy. Med Res Rev. 2010 published online 1 March 2010. In depth review of aurora A kinase, covering structure, expression, transcription, protein interactions, signaling and therapeutic inhibition.
10.1002/med.20203 16. Gautschi O, Heighway J, Mack PC, et al. Aurora kinases as anticancer drug targets. Clin Cancer Res. 2008, 14:1639 48. 17. Ujhazy P, Stewart D. DNA Repair. J Thorac Oncol. 2009, 11:S1068 70. 18. Smith SL, Bowers NL, Betticher DC, et al. Overexpression of aurora B kinase 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, 93:719 29. 19. Keen M, Taylor S. Mitotic drivers inhibitors of the aurora B kinase. Cancer Metastasis Rev. 2009, 28:185 95. 20. Mountzios G, Terpos E, Dimopoulos M A. Aurora kinases as targets for cancer therapy. Cancer Treat Rev. 2008, 34:175 82. 21. Mazumdar A, Henderson

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