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

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

Research output: Contribution to journal › Article › peer-review

46 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 language	English (US)
Pages (from-to)	1867-1871
Number of pages	5
Journal	Anticancer research
Volume	29
Issue number	6
State	Published - Jun 2009
Externally published	Yes

Keywords

Chordoma
mTOR
PI-103
PI3K

ASJC Scopus subject areas

Cancer Research
Oncology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. / Schwab, Joseph; Antonescu, Cristina; Boland, Patrick; Healey, John; Rosenberg, Andrew; Nielsen, Petur; Iafrate, John; Delaney, Thomas; Yoon, Sam; Choy, Edwin; Harmon, David; Raskin, Kevin; Yang, Cao; Mankin, Henry; Springfield, Dempsey; Hornicek, Francis; Duan, Zhenfeng.

In: Anticancer research, Vol. 29, No. 6, 06.2009, p. 1867-1871.

Research output: Contribution to journal › Article › peer-review

Schwab, Joseph ; Antonescu, Cristina ; Boland, Patrick ; Healey, John ; Rosenberg, Andrew ; Nielsen, Petur ; Iafrate, John ; Delaney, Thomas ; Yoon, Sam ; Choy, Edwin ; Harmon, David ; Raskin, Kevin ; Yang, Cao ; Mankin, Henry ; Springfield, Dempsey ; Hornicek, Francis ; Duan, Zhenfeng. / Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma. In: Anticancer research. 2009 ; Vol. 29, No. 6. pp. 1867-1871.

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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.",

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AU - Schwab, Joseph

AU - Antonescu, Cristina

AU - Boland, Patrick

AU - Healey, John

AU - Rosenberg, Andrew

AU - Nielsen, Petur

AU - Iafrate, John

AU - Delaney, Thomas

AU - Yoon, Sam

AU - Choy, Edwin

AU - Harmon, David

AU - Raskin, Kevin

AU - Yang, Cao

AU - Mankin, Henry

AU - Springfield, Dempsey

AU - Hornicek, Francis

AU - Duan, Zhenfeng

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N2 - 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.

AB - 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.

KW - Chordoma

KW - mTOR

KW - PI-103

KW - PI3K

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Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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