Display options
Cite
Purcell JW, Davis J, Reddy M, et al. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clin Cancer Res. 2010;16(2):566-76doi: 10.1158/1078-0432.CCR-09-1498.
Purcell, J. W., Davis, J., Reddy, M., Martin, S., Samayoa, K., Vo, H., Thomsen, K., Bean, P., Kuo, W. L., Ziyad, S., Billig, J., Feiler, H. S., Gray, J. W., Wood, K. W., & Cases, S. (2010). Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clinical cancer research : an official journal of the American Association for Cancer Research, 16(2), 566-76. https://doi.org/10.1158/1078-0432.CCR-09-1498
Purcell, James W, et al. "Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer." Clinical cancer research : an official journal of the American Association for Cancer Research vol. 16,2 (2010): 566-76. doi: https://doi.org/10.1158/1078-0432.CCR-09-1498
Purcell JW, Davis J, Reddy M, Martin S, Samayoa K, Vo H, Thomsen K, Bean P, Kuo WL, Ziyad S, Billig J, Feiler HS, Gray JW, Wood KW, Cases S. Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer. Clin Cancer Res. 2010 Jan 15;16(2):566-76. doi: 10.1158/1078-0432.CCR-09-1498. Epub 2010 Jan 12. PMID: 20068098; PMCID: PMC2844774.
Copy Download .nbib Format: NLM
Share it on

Clin Cancer Res. 2010 Jan 15;16(2):566-76. doi: 10.1158/1078-0432.CCR-09-1498. Epub 2010 Jan 12.

Activity of the kinesin spindle protein inhibitor ispinesib (SB-715992) in models of breast cancer.

Clinical cancer research : an official journal of the American Association for Cancer Research

James W Purcell, Jefferson Davis, Mamatha Reddy, Shamra Martin, Kimberly Samayoa, Hung Vo, Karen Thomsen, Peter Bean, Wen Lin Kuo, Safiyyah Ziyad, Jessica Billig, Heidi S Feiler, Joe W Gray, Kenneth W Wood, Sylvaine Cases

Affiliations

  1. Cytokinetics, Inc., South San Francisco, California 94080, USA.

PMID: 20068098 PMCID: PMC2844774 DOI: 10.1158/1078-0432.CCR-09-1498

Abstract

PURPOSE: Ispinesib (SB-715992) is a potent inhibitor of kinesin spindle protein, a kinesin motor protein essential for the formation of a bipolar mitotic spindle and cell cycle progression through mitosis. Clinical studies of ispinesib have shown a 9% response rate in patients with locally advanced or metastatic breast cancer and a favorable safety profile without significant neurotoxicities, gastrointestinal toxicities, or hair loss. To better understand the potential of ispinesib in the treatment of breast cancer, we explored the activity of ispinesib alone and in combination with several therapies approved for the treatment of breast cancer.

EXPERIMENTAL DESIGN: We measured the ispinesib sensitivity and pharmacodynamic response of breast cancer cell lines representative of various subtypes in vitro and as xenografts in vivo and tested the ability of ispinesib to enhance the antitumor activity of approved therapies.

RESULTS: In vitro, ispinesib displayed broad antiproliferative activity against a panel of 53 breast cell lines. In vivo, ispinesib produced regressions in each of five breast cancer models and tumor-free survivors in three of these models. The effects of ispinesib treatment on pharmacodynamic markers of mitosis and apoptosis were examined in vitro and in vivo, revealing a greater increase in both mitotic and apoptotic markers in the MDA-MB-468 model than in the less sensitive BT-474 model. In vivo, ispinesib enhanced the antitumor activity of trastuzumab, lapatinib, doxorubicin, and capecitabine and exhibited activity comparable with paclitaxel and ixabepilone.

CONCLUSIONS: These findings support further clinical exploration of kinesin spindle protein inhibitors for the treatment of breast cancer.

References

  1. Anticancer Res. 2007 Jul-Aug;27(4B):2279-87 - PubMed
  2. J Clin Oncol. 1999 Aug;17(8):2355-64 - PubMed
  3. Mol Cell Biol. 2007 Jan;27(2):689-98 - PubMed
  4. J Clin Oncol. 2005 Jun 1;23(16):3676-85 - PubMed
  5. J Clin Oncol. 2007 Aug 10;25(23):3421-7 - PubMed
  6. Cancer Res. 2002 Oct 15;62(20):5703-10 - PubMed
  7. Nat Rev Cancer. 2007 Feb;7(2):107-17 - PubMed
  8. Cancer Cell. 2008 Aug 12;14(2):111-22 - PubMed
  9. Cell. 1995 Dec 29;83(7):1159-69 - PubMed
  10. Cancer Cell. 2006 Dec;10(6):515-27 - PubMed
  11. Invest New Drugs. 2008 Jun;26(3):257-64 - PubMed
  12. Br J Cancer. 1999 Feb;79(5-6):707-17 - PubMed
  13. Cancer Res. 2008 Jul 1;68(13):5380-9 - PubMed
  14. J Clin Oncol. 2007 Aug 10;25(23):3407-14 - PubMed
  15. Cell. 1991 Sep 20;66(6):1197-206 - PubMed
  16. Cancer Res. 2008 May 1;68(9):3269-76 - PubMed
  17. Oncogene. 2006 Nov 23;25(55):7245-59 - PubMed
  18. Oncologist. 2006 Nov-Dec;11(10):1047-57 - PubMed
  19. J Natl Cancer Inst. 1991 Jun 5;83(11):757-66 - PubMed
  20. Biochemistry. 2008 Mar 18;47(11):3576-85 - PubMed
  21. Cancer Res. 1998 Apr 15;58(8):1609-15 - PubMed
  22. Semin Oncol. 1993 Aug;20(4 Suppl 3):1-15 - PubMed
  23. Invest New Drugs. 2008 Jun;26(3):249-55 - PubMed
  24. J Cell Sci. 2009 Aug 1;122(Pt 15):2579-85 - PubMed
  25. Oncologist. 2001;6 Suppl 3:5-12 - PubMed
  26. Cancer Cell. 2005 Jul;8(1):49-59 - PubMed
  27. Cancer Res. 2004 May 1;64(9):3276-80 - PubMed
  28. Cancer Res. 1998 Jul 1;58(13):2825-31 - PubMed
  29. Ann Oncol. 2008 Feb;19(2):212-22 - PubMed
  30. N Engl J Med. 2001 Mar 15;344(11):783-92 - PubMed
  31. Nature. 1992 Oct 8;359(6395):540-3 - PubMed
  32. Invest New Drugs. 2008 Jun;26(3):265-72 - PubMed
  33. Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5386-90 - PubMed
  34. Cytometry. 1998 Jun 1;32(2):71-7 - PubMed

Substances

MeSH terms

Publication Types

Grant support