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Sarcoma
Volume 2012, Article ID 680708, 8 pages
http://dx.doi.org/10.1155/2012/680708
Research Article

Efficacy of Phosphatidylinositol-3 Kinase Inhibitors in a Primary Mouse Model of Undifferentiated Pleomorphic Sarcoma

1Department of Radiation Oncology, Duke University Medical Center, Box 91006, Durham, NC 27710, USA
2Department of Radiation Oncology, Boramae Hospital, Seoul National University Hospital, Seoul 156-707, Republic of Korea
3Department of Pharmacology and Cancer Biology, Duke University Medical Center, Box 91006, Durham, NC 27710, USA
4Department of Clinical Pathology, College of Veterinary Medicine, Seoul National University, Seoul 156-707, Republic of Korea
5Division of Medical Oncology, Duke University Medical Center, Box 91006, Durham, NC 27710, USA

Received 4 January 2012; Revised 10 February 2012; Accepted 13 February 2012

Academic Editor: Luca Sangiorgi

Copyright © 2012 Suzy Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. P. Lorigan, J. Verweij, Z. Papai et al., “Phase III trial of two investigational schedules of ifosfamide compared with standard-dose doxorubicin in advanced or metastatic soft tissue sarcoma: a European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group study,” Journal of Clinical Oncology, vol. 25, no. 21, pp. 3144–3150, 2007. View at Publisher · View at Google Scholar · View at Scopus
  2. V. H. C. Bramwell, D. Anderson, and M. L. Charette, “Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: a meta-analysis and clinical practice guideline,” Sarcoma, vol. 4, no. 3, pp. 103–112, 2000. View at Google Scholar · View at Scopus
  3. J. Barretina, B. S. Taylor, S. Banerji et al., “Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy,” Nature Genetics, vol. 42, no. 8, pp. 715–721, 2010. View at Publisher · View at Google Scholar · View at Scopus
  4. M. C. Manara, G. Nicoletti, D. Zambelli et al., “NVP-BEZ235 as a new therapeutic option for sarcomas,” Clinical Cancer Research, vol. 16, no. 2, pp. 530–540, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. D. G. Kirsch, D. M. Dinulescu, J. B. Miller et al., “A spatially and temporally restricted mouse model of soft tissue sarcoma,” Nature Medicine, vol. 13, no. 8, pp. 992–997, 2007. View at Publisher · View at Google Scholar · View at Scopus
  6. J. K. Mito, R. F. Riedel, L. Dodd et al., “Cross species genomic analysis identifies a mouse model as undifferentiated pleomorphic sarcoma/malignant fibrous histiocytoma,” PloS One, vol. 4, no. 11, Article ID e8075, 2009. View at Google Scholar · View at Scopus
  7. J. A. Engelman, “Targeting PI3K signalling in cancer: opportunities, challenges and limitations,” Nature Reviews Cancer, vol. 9, no. 8, pp. 550–562, 2009. View at Publisher · View at Google Scholar · View at Scopus
  8. I. Barone, L. Brusco, G. Gu et al., “Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor α,” Journal of the National Cancer Institute, vol. 103, no. 7, pp. 538–552, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. N. E. Sharpless and R. A. de Pinho, “The mighty mouse: genetically engineered mouse models in cancer drug development,” Nature Reviews Drug Discovery, vol. 5, no. 9, pp. 741–754, 2006. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Singh, A. Lima, R. Molina et al., “Assessing therapeutic responses in Kras mutant cancers using genetically engineered mouse models,” Nature Biotechnology, vol. 28, no. 6, pp. 585–593, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. V. Serra, B. Markman, M. Scaltriti et al., “NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations,” Cancer Research, vol. 68, no. 19, pp. 8022–8030, 2008. View at Publisher · View at Google Scholar · View at Scopus
  12. C. Santiskulvong, G. E. Konecny, M. Fekete et al., “Dual targeting of phosphoinositide 3-kinase and mammalian target of rapamycin using NVP-BEZ235 as a novel therapeutic approach in human ovarian carcinoma,” Clinical Cancer Research, vol. 17, no. 8, pp. 2373–2384, 2011. View at Publisher · View at Google Scholar · View at Scopus
  13. R. Marone, D. Erhart, A. C. Mertz et al., “Targeting melanoma with dual phosphoinositide 3-kinase/mammalian target of rapamycin inhibitors,” Molecular Cancer Research, vol. 7, no. 4, pp. 601–613, 2009. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Fuereder, T. Wanek, P. Pflegerl et al., “Gastric cancer growth control by BEZ235 in vivo does not correlate with PI3K/mTOR target inhibition but with [18F]FLT uptake,” Clinical Cancer Research, vol. 17, no. 16, pp. 5322–5332, 2011. View at Publisher · View at Google Scholar
  15. M. Masuda, M. Shimomura, K. Kobayashi et al., “Growth inhibition by NVP-BEZ235, a dual PI3K/mTOR inhibitor, in hepatocellular carcinoma cell lines,” Oncology Reports, vol. 26, no. 5, pp. 1273–1279, 2011. View at Publisher · View at Google Scholar
  16. D. C. Cho, M. B. Cohen, D. J. Panka et al., “The efficacy of the novel dual PI3-kinase/mTOR inhibitor NVP-BEZ235 compared with rapamycin in renal cell carcinoma,” Clinical Cancer Research, vol. 16, no. 14, pp. 3628–3638, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. A. Dubrovska, J. Elliott, R. J. Salamone et al., “Combination therapy targeting both tumor-initiating and differentiated cell populations in prostate carcinoma,” Clinical Cancer Research, vol. 16, no. 23, pp. 5692–5702, 2010. View at Publisher · View at Google Scholar · View at Scopus
  18. S. M. Maira, F. Stauffer, J. Brueggen et al., “Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity,” Molecular Cancer Therapeutics, vol. 7, no. 7, pp. 1851–1863, 2008. View at Publisher · View at Google Scholar · View at Scopus
  19. A. P. Bhatt, P. M. Bhende, S. H. Sin, D. Roy, D. P. Dittmer, and B. Damania, “Dual inhibition of PI3K and mTOR inhibits autocrine and paracrine proliferative loops in PI3K/Akt/mTOR-addicted lymphomas,” Blood, vol. 115, no. 22, pp. 4455–4463, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. T. J. Liu, D. Koul, T. LaFortune et al., “NVP-BEZ235, a novel dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor, elicits multifaceted antitumor activities in human gliomas,” Molecular Cancer Therapeutics, vol. 8, no. 8, pp. 2204–2210, 2009. View at Publisher · View at Google Scholar · View at Scopus
  21. C. X. Xu, Y. Li, P. Yue et al., “The combination of RAD001 and NVP-BEZ235 exerts synergistic anticancer activity against non-small cell lung cancer in vitro and in vivo,” PloS One, vol. 6, no. 6, Article ID e20899, 2011. View at Publisher · View at Google Scholar · View at Scopus
  22. J. A. Engelman, L. Chen, X. Tan et al., “Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers,” Nature Medicine, vol. 14, no. 12, pp. 1351–1356, 2008. View at Publisher · View at Google Scholar · View at Scopus