Translational modeling and simulation approaches for molecularly targeted small molecule anticancer agents from bench to bedside

Expert Opinion on Drug Metabolism & Toxicology
Shinji YamazakiP Vicini

Abstract

Recent advances in molecular biology have enabled personalized cancer therapies with molecularly targeted agents (MTAs), which offer a promising future for cancer therapy. Dynamic modeling and simulation (M&S) is a powerful mathematical approach linking drug exposures to pharmacological responses, providing a quantitative assessment of in vivo drug potency. Accordingly, a growing emphasis is being placed upon M&S to quantitatively understand therapeutic exposure-response relationships of MTAs in nonclinical models. An overview of M&S approaches for MTAs in nonclinical models is presented with discussion about mechanistic extrapolation of antitumor efficacy from bench to bedside. Emphasis is placed upon recent advances in M&S approaches linking drug exposures, biomarker responses (e.g. target modulation) and pharmacological outcomes (e.g. antitumor efficacy). For successful personalized cancer therapies with MTAs, it is critical to mechanistically and quantitatively understand their exposure-response relationships in nonclinical models, and to logically and properly apply such knowledge to the clinic. Particularly, M&S approaches to predict pharmacologically active concentrations of MTAs in patients based upon nonclinical data w...Continue Reading

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Citations

Feb 26, 2020·The Journal of Pharmacology and Experimental Therapeutics·Shinji YamazakiShikhar Sharma
Jun 23, 2020·Clinical Pharmacology and Therapeutics·James W T YatesPaolo Vicini
Apr 14, 2018·BMC Cancer·Claire Jean-QuartierAndreas Holzinger
Jun 27, 2017·NPJ Systems Biology and Applications·Daniel C KirouacSaroja Ramanujan
Jul 1, 2017·Cancer Chemotherapy and Pharmacology·Wan-Su ParkDong-Seok Yim

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