Speaker
Description
Quantitative systems pharmacology (QSP) models are increasingly used to inform dose scheduling in oncology. Standard tumour growth inhibition models typically combine empirical growth laws with drug action functions. Recent work suggests that non-uniform dosing regimens may outperform uniform dosing regimens.
Here we present a systematic evaluation of how modelling choices on growth law and kill function influence optimal dosing strategies. The results reveal that predicted optimal dosing strategies depend strongly on the underlying model assumptions and parameter selection. When the drug action is nonlinear, the preferred dosing regimen depends on the mean drug concentration.
To evaluate these predictions using experimental data, we analysed tumour growth trajectories from patient-derived xenograft (PDX) models used in pre-clinical cytotoxic chemotherapy studies \cite{Ref1}. This data spans a wide range of tumour growth kinetics, allowing us to estimate parameter regimes representing fast and slow growing tumours. Incorporating these empirically derived growth dynamics into the modelling framework reveals the sensitivity of the optimal dosing strategy to the growth rate of the tumour. Fast-growing tumours favour different dosing regimens than slow growing tumours based on the underlying tumour growth model. These findings highlight the importance of integrating experimental growth data when using mechanistic models to inform dosing strategies.
Bibliography
@article{Ref1,
title = {High-throughput screening using patient-derived tumor xenografts to predict clinical trial drug response},
volume = {21},
issn = {1078-8956, 1546-170X},
url = {https://www.nature.com/articles/nm.3954},
doi = {10.1038/nm.3954},
language = {en},
number = {11},
urldate = {2026-03-13},
journal = {Nature Medicine},
author = {Gao, Hui and Korn, Joshua M and Ferretti, Stéphane and Monahan, John E and Wang, Youzhen and Singh, Mallika and Zhang, Chao and Schnell, Christian and Yang, Guizhi and Zhang, Yun and Balbin, O Alejandro and Barbe, Stéphanie and Cai, Hongbo and Casey, Fergal and Chatterjee, Susmita and Chiang, Derek Y and Chuai, Shannon and Cogan, Shawn M and Collins, Scott D and Dammassa, Ernesta and Ebel, Nicolas and Embry, Millicent and Green, John and Kauffmann, Audrey and Kowal, Colleen and Leary, Rebecca J and Lehar, Joseph and Liang, Ying and Loo, Alice and Lorenzana, Edward and Robert McDonald, E and McLaughlin, Margaret E and Merkin, Jason and Meyer, Ronald and Naylor, Tara L and Patawaran, Montesa and Reddy, Anupama and Röelli, Claudia and Ruddy, David A and Salangsang, Fernando and Santacroce, Francesca and Singh, Angad P and Tang, Yan and Tinetto, Walter and Tobler, Sonja and Velazquez, Roberto and Venkatesan, Kavitha and Von Arx, Fabian and Wang, Hui Qin and Wang, Zongyao and Wiesmann, Marion and Wyss, Daniel and Xu, Fiona and Bitter, Hans and Atadja, Peter and Lees, Emma and Hofmann, Francesco and Li, En and Keen, Nicholas and Cozens, Robert and Jensen, Michael Rugaard and Pryer, Nancy K and Williams, Juliet A and Sellers, William R},
month = nov,
year = {2015},
pages = {1318--1325},
}
