American Association for Cancer Research
00085472can131528-sup-tab2.pdf (78.21 kB)

Supplementary Table 2 from A Circadian Clock Transcription Model for the Personalization of Cancer Chronotherapy

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journal contribution
posted on 2023-03-30, 22:14 authored by Xiao-Mei Li, Ali Mohammad-Djafari, Mircea Dumitru, Sandrine Dulong, Elisabeth Filipski, Sandrine Siffroi-Fernandez, Ali Mteyrek, Francesco Scaglione, Catherine Guettier, Franck Delaunay, Francis Lévi

PDF file - 78K, Plasma pharmacokinetic parameters (Mean plus/minus SEM) of irinotecan according to timing and chronotoxicity classes.



Circadian timing of anticancer medications has improved treatment tolerability and efficacy several fold, yet with intersubject variability. Using three C57BL/6-based mouse strains of both sexes, we identified three chronotoxicity classes with distinct circadian toxicity patterns of irinotecan, a topoisomerase I inhibitor active against colorectal cancer. Liver and colon circadian 24-hour expression patterns of clock genes Rev-erbα and Bmal1 best discriminated these chronotoxicity classes, among 27 transcriptional 24-hour time series, according to sparse linear discriminant analysis. An 8-hour phase advance was found both for Rev-erbα and Bmal1 mRNA expressions and for irinotecan chronotoxicity in clock-altered Per2m/m mice. The application of a maximum-a-posteriori Bayesian inference method identified a linear model based on Rev-erbα and Bmal1 circadian expressions that accurately predicted for optimal irinotecan timing. The assessment of the Rev-erbα and Bmal1 regulatory transcription loop in the molecular clock could critically improve the tolerability of chemotherapy through a mathematical model–based determination of host-specific optimal timing. Cancer Res; 73(24); 7176–88. ©2013 AACR.