Parallel PI3K, AKT and mTOR inhibition is required to control feedback loops that limit tumor therapy.

ABSTRACT: Targeting the PI3K pathway has achieved limited success in cancer therapy. One reason for the disappointing activity of drugs that interfere with molecules that are important player in this pathway is the induction of multiple feedback loops that have been only partially understood. To understand these limitations and develop improved treatment strategies, we comprehensively characterized molecular mechanisms of PI3K pathway signaling in bladder cancer cell lines upon using small molecule inhibitors and RNAi technologies against all key molecules and protein complexes within the pathway and analyzed functional and molecular consequences. When targeting either mTORC1, mTOR, AKT or PI3K, only S6K1 phosphorylation was affected in most cell lines examined. Dephosphorylation of 4E-BP1 required

SUBMITTER: Sathe A 

PROVIDER: S-EPMC5777650 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature