Single cell phosphoproteomics identifies adaptive network dynamics of mTOR inhibitor resistance and defines effective combination therapy in glioblastoma

Abstract

Resistance to single-agent targeted cancer therapy is almost universal. Resistance can occur when drug-resistant tumor cell subpopulations expand to drive recurrence in a process akin to Darwinian-type evolution under the selection pressure of the drug. An alternative resistance mechanism is the one in which cancer cells targeted by the inhibitor adapt to that drug, so as to maintain the signal flux through those networks that are required for tumor maintenance and growth. The main goal of this study is to identify the mechanisms of resistance in a targeted therapy by analyzing single cells and to provide a strategy to design a more effective therapy that suppresses resistance.

Files

Additional details