Single-Cell Pharmacodynamic Monitoring of S6 Ribosomal Protein Phosphorylation in AML Blasts during a Clinical Trial Combining the mTOR Inhibitor Sirolimus and Intensive Chemotherapy

Abstract

The methodology described is rapid and reproducible. We show the feasibility of real-time, direct pharmacodynamic monitoring by flow cytometry during clinical trials combining intensive chemotherapy and signal transduction inhibitors. This approach greatly clarifies pharmacokinetic/pharmacodynamic relationships and has broad application to preclinical and clinical testing of drugs whose direct or downstream effects disrupt PI3K/AKT/mTOR signaling.