Purpose: Because we recently identified Akt activation as a novel poor prognostic indicator in neuroblastoma, we investigated whether phosphoinositide 3 0 -kinase (PI3K) inhibition sensitizes neuroblastoma cells for TRAIL-induced apoptosis.Experimental Design: The effect of pharmacological or genetic inhibition of PI3K or mTOR was analyzed on apoptosis induction, clonogenic survival, and activation of apoptosis signaling pathways in vitro and in a neuroblastoma in vivo model. The functional relevance of individual Bcl-2 family proteins was examined by knockdown or overexpression experiments.Results: The PI3K inhibitor PI103 cooperates with TRAIL to synergistically induce apoptosis (combination index < 0
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