A Circadian Clock Transcription Model for the Personalization of Cancer Chronotherapy

Circadian timing of irinotecan may improve treatment tolerability and efficacy several fold.

• Three chronotoxicity classes were identified based on distinct circadian toxicity patterns of irinotecan in mouse strains.
• Liver and colon expression patterns of the clock genes Rev-erbα and Bmal1 were key in discriminating these chronotoxicity classes.
• An 8-hour phase advance was observed for both Rev-erbα and Bmal1 mRNA expressions and for irinotecan chronotoxicity in specific mice.
• A linear model based on Rev-erbα and Bmal1 expressions may accurately predict optimal irinotecan timing.
• The regulatory loop involving Rev-erbα and Bmal1 could enhance chemotherapy tolerability through tailored timing strategies.

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