HesseMuellerRelogio2023 - Timing treatment toxicity of the cancer drug irinotecan based on circadian gene expression profiles

Chronotherapy demands that patients are treated at a particular time of the day in order to maximize treatment effects and minimize side effects. Chronotherapy can be personalized by taking into account the patient's circadian rhythm as measured by a repetitive sampling of gene expression over the day. As a proof of concept, the submitted model links circadian gene expression to the diurnal toxicity profile of the cancer drug irinotecan. The model is based on MODEL2109140001; it implements a transcription-translation network model of the core clock and additional genes associated with irinotecan metabolism and links this to a model of the pharmacokinetics and -dynamics (PK-PD) of irinotecan. The submitted model refines network connections of the gene regulatory network and adds a treatment-induced increase in UGT1A1 and a transient increase in the apoptosis rate in response to treatment for the PK-PD part.