Table 1.

Combination strategies through EGFR-PI3K-mTOR axis to improve therapeutic efficacy

Agent	Targets	Biological Effects
Erlotnib + mTOR	EGFR, mTOR	Antiproliferative
Erlotnib + PI3K/mTOR	EGFR, p110α, mTOR	Antiproliferative
shAkt123 + hyroxychloroquine	Akt, lysosomotropic	Antiproliferative, apoptosis?
PI3K/mTOR + temozolomide	p110α, mTOR, nonspecifc	Antiproliferative, apoptosis?
PI3K/mTOR + radiation	p110α, mTOR, nonspecifc	Antiproliferative, apoptosis?

Combination strategies to target multiple nodes within the EGFR-PI3K-mTOR network. Combining kinase inhibitors with cytotoxic chemotherapy, radiation, and with inhibitors off autophagy may improve the therapeutic efficacy. Whether these approaches show improved efficacy and whether their use is associated with acceptable levels of toxicity are areas of active basic and clinical investigation. A number of allosteric inhibitors of mTORC1 and dual inhibitors of PI3K and mTOR are currently being tested clinically. See text for details