p70S6 kinase phosphorylation for pharmacodynamic monitoring

Inhibitors of the mammalian target of rapamycin (mTOR) are administered as immunosuppressant as well as antineoplastic agents. Because of the narrow therapeutic index of mTOR inhibitors, drug monitoring is required, and this is usually done by measuring blood drug levels. Increasing knowledge of the signaling pathways of the mTOR protein kinase provides an opportunity for pharmacodynamic drug monitoring.With the different laboratory methods it is becoming possible to measure new biomarkers to control the influence of mTOR activity. One of these biomarkers is phospho-S6 kinase, with its isoform p70S6K.

► mTOR inhibitors are administered as immunosuppressant or as antineoplastic agents.
► mTOR inhibitors have a narrow therapeutic index and drug monitoring is required.
► Trough level measurements of mTOR inhibitors are not sufficient for drug monitoring.
► Knowledge of the mTOR pathways makes a pharmacodynamics drug monitoring possible.
► p70S6K is a biomarker for pharmacodynamic monitoring of mTOR inhibitors.