Quantitative Systems Pharmacology Approaches for Immuno-Oncology: Adding Virtual Patients to the Development Paradigm.

Clinical Pharmacology and Therapeutics
Vijayalakshmi ChelliahAndrzej M. Kierzek

Abstract

Drug development in oncology commonly exploits the tools of molecular biology to gain therapeutic benefit through reprograming of cellular responses. In immuno-oncology (IO) the aim is to direct the patient's own immune system to fight cancer. After remarkable successes of antibodies targeting PD1/PD-L1 and CTLA4 receptors in targeted patient populations, the focus of further development has shifted toward combination therapies. However, the current drug-development approach of exploiting a vast number of possible combination targets and dosing regimens has proven to be challenging and is arguably inefficient. In particular, the unprecedented number of clinical trials testing different combinations may no longer be sustainable by the population of available patients. Further development in IO requires a step change in selection and validation of candidate therapies to decrease development attrition rate and limit the number of clinical trials. Quantitative systems pharmacology (QSP) proposes to tackle this challenge through mechanistic modeling and simulation. Compounds' pharmacokinetics, target binding, and mechanisms of action as well as existing knowledge on the underlying tumor and immune system biology are described by qua...Continue Reading

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Citations

Sep 30, 2020·Cancer Control : Journal of the Moffitt Cancer Center·Robert A BeckmanFrederick R Adler
Aug 11, 2021·Pharmaceutics·Aymara Sancho-AraizIñaki F Trocóniz
Aug 1, 2021·CPT: Pharmacometrics & Systems Pharmacology·Mario GiorgiAndrzej M Kierzek
Aug 10, 2021·Frontiers in Bioengineering and Biotechnology·Virginia CazzagonFrancesco Gonella

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