Quantitative systems pharmacology (QSP)
Mechanistic computer models that join a drug's pharmacology to the biology of the tumour and the body, used by developers and regulators to pick doses, predict combinations and explain why a trial failed.
Overview
Quantitative systems pharmacology couples pharmacokinetics with mechanistic models of signalling pathways, cell populations and organ systems. In oncology it has been used to predict the exposure-response of checkpoint inhibitors, to design bispecific and CAR-T dosing that limits cytokine release, to simulate resistance to targeted drugs and to support regulatory submissions under the FDA's model-informed drug development programme. Project Optimus, the FDA's 2021 initiative to end maximum-tolerated-dose defaults for targeted drugs, leans on these models to justify lower doses.
How it works
Systems of differential equations link drug concentration to receptor occupancy, pathway activity, cell kill and clinical markers, calibrated to preclinical and clinical data and used to simulate untested regimens.
- Accepted by regulators for dose justification
- Predicts combinations before trials
- Integrates disparate data
- Large models are hard to validate
- Parameter uncertainty is often understated
- Expertise concentrated in industry
Latest papers
topQuery for this technology: (TITLE:"Quantitative systems pharmacology" OR ABSTRACT:"Quantitative systems pharmacology") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Quantitative systems pharmacology (QSP), not a curated reading list.
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