. Author manuscript; available in PMC: 2010 Dec 11.

Published in final edited form as: Sci Signal. 2010 Nov 9;3(147):ra81. doi: 10.1126/scisignal.2001017

Table 1.

Summary of combination therapies targeting the PI3K-Akt-mTOR and autophagic pathways to induce apoptosis in glioma.

Agent	Target	Reference	Agent status	Results
PI-103	PI3K and mTOR catalytic site	(28–30)	Preclinical	Induced autophagy. Cooperated with Baf A1 and monensin individually to induce apoptosis.
PIK-90	PI3K	(29)	Preclinical	Induced autophagy weakly. Cytostatic in combination with rapamycin or Baf A1. Apoptosis required rapamycin, PIK-90, and Baf A1 in combination.
AktI-1/2	PH domain of Akt1 and Akt2	(43)	Preclinical	Induced autophagy weakly. Cytostatic in combination with Baf A1. Apoptosis required AktI-1/2, rapamycin, and Baf A1 in combination.
Rapamycin	mTORC1	(45)	Clinical trials	Induced autophagy. Stimulated Akt phosphorylation. Cytostatic in combination with PIK-90 or Baf A1. Apoptosis required rapamycin, PIK-90, and Baf A1 in combination.
NVP-BEZ235	PI3K and mTOR catalytic site	(64)	Clinical trials	Induced autophagy. Cooperated with chloroquine to induce apoptosis.
Ku-0063794	mTOR catalytic site	(46)	Preclinical	Induced autophagy. Cooperated with Baf A1 to induce apoptosis.
3MA	hVps34 (blocks autophagosome formation)	(35)	Preclinical	Cooperated with PI-103 to induce apoptosis.
Baf A1	Vacuolar type H⁺-ATPase (blocks autophagosome maturation)	(31)	Preclinical	Cooperated with PI-103 to induce apoptosis.
Monensin	Na⁺/H⁺ antiporter (blocks autophagosome maturation)	(38)	Preclinical	Cooperated with PI-103 to induce apoptosis.
Chloroquine	Heme crystallization (blocks autophagosome maturation)	(63)	Clinical	Cooperated with NVP-BEZ235 to induce apoptosis.