Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma

Joseph Schwab, Cristina Antonescu, Patrick Boland, John Healey, Andrew Rosenberg, Petur Nielsen, John Iafrate, Thomas Delaney, Sam Yoon, Edwin Choy, David Harmon, Kevin Raskin, Cao Yang, Henry Mankin, Dempsey Springfield, Francis Hornicek, Zhenfeng Duan

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43 Scopus citations

Abstract

Background: Chordomas are rare tumors of the axial skeleton for which surgical resection remains the most reliable means of cure. PI-103 is a inhibitor of PI3K/AKT and mTOR activation. This study aims to determine whether the PI3K/mTOR pathway was active in chordomas and whether their inhibition could lead to decreased proliferation and increased apoptosis. Materials and Methods: Thirteen human chordoma were tested for activation of the PI3K/mTOR pathway. The human chordoma cell line UCH-1 was treated with increasing doses of PI-103. Inhibition of AKT and mTOR was examined and assays assessing proliferation and apoptosis were performed. Results: The chordoma specimen demonstrated activation of the PI3K/mTOR pathway. PI-103 inhibited the AKT and mTOR activation in the UCH-1 cell line. PI-103 inhibited proliferation and induced apoptosis in UCH-1. Conclusion: The PI3K/AKT and mTOR signaling pathway is constitutively activated in chordoma. PI-103 decreases proliferation and induces apoptosis in the UCH-1 via inhibition of the PI3K/mTOR pathway.

Original languageEnglish (US)
Pages (from-to)1867-1871
Number of pages5
JournalAnticancer research
Volume29
Issue number6
StatePublished - Jun 1 2009

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Keywords

  • Chordoma
  • mTOR
  • PI-103
  • PI3K

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Schwab, J., Antonescu, C., Boland, P., Healey, J., Rosenberg, A., Nielsen, P., Iafrate, J., Delaney, T., Yoon, S., Choy, E., Harmon, D., Raskin, K., Yang, C., Mankin, H., Springfield, D., Hornicek, F., & Duan, Z. (2009). Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. Anticancer research, 29(6), 1867-1871.