Combination of PI3K/mTOR inhibition demonstrates efficacy in human chordoma
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.
Anticancer Research 29(6): 1867-1871
2009
ISSN/ISBN: 0250-7005 PMID: 19528441 Document Number: 635261
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. 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. 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. 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.