Andarine Androgen Receptor inhibitor combination with radiation therapy results in enhanced killing of androgen

combination with radiation therapy results in enhanced killing of androgen insensitive prostate cancer cells and may ultimately have the potential to improve the cure rate for patients with locally advanced prostate cancer. Further studies are warranted to assess the in vivo and clinical efficacy of AZD1152 in the treatment of hormone refractory prostate cancer. Acknowledgments Andarine Androgen Receptor inhibitor We would like to thank Jiaqing Li for his laboratory assistance. This work was supported in part by U.S. Department of Defense Grant DOD W23RYX 3305 N603 and Vanderbilt CTSA grant 1 UL1 RR024975 from NCRR/NIH. References 1. Cancer Facts and Figures 2008. American Cancer Society, Atlanta: 2008. 2. Adams RR, Maiato H, Earnshaw WC, Carmena M.
Essential roles of Drosophila inner centromere protein and aurora B in histone H3 phosphorylation, metaphase chromosome alignment, kinetochore disjunction, and chromosome segregation. J Cell Biol. 2001, 153:865 880. Niermann et al. Page 7 Radiat Res. Author manuscript, available in PMC 2012 April 1. NIH PA Author Manuscript NIH PA Author Manuscript NIH PA Author Manuscript 3. Hauf S, Cole CYC202 CDK inhibitor RW, LaTerra S, Zimmer C, Schnapp G, Walter R, Heckel A, van Meel J, Rieder CL, Peters JM. The small molecule Hesperadin reveals a role for Aurora B in correcting kinetochoremicrotubule attachment and in maintaining the spindle assembly checkpoint. J Cell Biol. 2003, 161:281 294. 4. Andrews PD, Knatko E, Moore WJ, Swedlow JR. Mitotic mechanics: the auroras come into view. Curr Opin Cell Biol. 2003, 15:672 683. 5. Altieri DC. Molecular circuits of apoptosis regulation and cell division control: the surviving paradigm.
J Cell Biochem. 2004, 92:656 663. 6. Carmena M, Earnshaw WC. The cellular geography of aurora kinases. Nat Rev Mol Cell Biol. 2003, 4:842 854. 7. Lee EC, Frolov A, Li R, Ayala G, Greenberg NM. Targeting Aurora kinases for the treatment of prostate cancer. Cancer Res. 2006, 66:4996 5002. 8. Chieffi P, Cozzolino L, Kisslinger A, Libertini S, Staibano S, Mansueto G, De Rosa G, Villacci A, Vitale M, Tramontano D. Aurora B expression directly correlates with prostate cancer malignancy and influence prostate cell proliferation. Prostate. 2006, 66:326 333. 9. Ota T, Suto S, Katayama H, Han ZB, Suzuki F, Maeda M, Tanino M, Terada Y, Tatsuka M. Increased mitotic phosphorylation of histone H3 attributable to AIM 1/Aurora B overexpression contributes to chromosome number instability.
Cancer Res. 2002, 62:5168 5177. 10. Araki K, Nozaki K, Ueba T, Tatsuka M, Hashimoto N. High expression of Aurora B/Aurora and Ipll like midbody associated protein in astrocytomas. J Neurooncol. 2004, 67:53 64. 11. Kulkarni AA, Loddo M, Leo E, Rashid M, Eward KL, Fanshawe TR, Butcher J, Frost A, Ledermann JA, Stoeber K. DNA replication licensing factors and aurora kinases are linked to aneuploidy and clinical outcome in epithelial ovarian carcinoma. Clin Cancer Res. 2007, 13:6153 6161. 12. Zeng WF, Navaratne K, Prayson RA, Weil RJ. Aurora B expression correlates with aggressive behaviour in glioblastoma multiforme. J Clin Pathol. 2007, 60:218 221. 13. Wilkinson RW, Odedra R, Heaton SP, Wedge SR, Keen NJ, Crafter C, Foster JR, Brady MC, Bigley A, Green S.
AZD1152, a selective inhibitor of Aurora B kinase, inhibits human tumor xenograft growth by inducing apoptosis. Clin Cancer Res. 2007, 13:3682 3688. 14. Tao Y, Zhang P, Girdler F, Frascogna V, Castedo M, Bourhis J, Kroemer G, Deutsch E. Enhancement of radiation response in p53 deficient cancer cells by the Aurora B kinase inhibitor AZD1152. Oncogene. 2008, 27:3244 3255. 15. Kim KW, Mutter RW, Willey CD, Subhawong TK, Shinohara ET, Albert JM, Ling G, Cao C, Gi YJ, Lu B. Inhibition of surviving and aurora B kinase sensitizes mesothelioma cells by enhancing mitotic arrests. Int J Radiat Oncol Biol Phys. 2007, 67:1519 1525. 16. 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 le

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