A mathematical model of the circadian clock and drug pharmacology to optimize irinotecan administration timing in colorectal cancer.

ABSTRACT: Scheduling anticancer drug administration over 24 h may critically impact treatment success in a patient-specific manner. Here, we address personalization of treatment timing using a novel mathematical model of irinotecan cellular pharmacokinetics and -dynamics linked to a representation of the core clock and predict treatment toxicity in a colorectal cancer (CRC) cellular model. The mathematical model is fitted to three different scenarios: mouse liver, where the drug metabolism mainly occurs, and two human colorectal cancer cell lines representing an in vitro experimental system for human colorectal cancer progression. Our model successfully recapitulates quantitative circadian datasets of mRNA and protein expression together with timing-dependent irinotecan cytotoxicity data. The

SUBMITTER: Hesse J 

PROVIDER: S-EPMC8477139 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature