| First Author | Li XM | Year | 2013 |
| Journal | Cancer Res | Volume | 73 |
| Issue | 24 | Pages | 7176-88 |
| PubMed ID | 24154875 | Mgi Jnum | J:206518 |
| Mgi Id | MGI:5551332 | Doi | 10.1158/0008-5472.CAN-13-1528 |
| Citation | Li XM, et al. (2013) A circadian clock transcription model for the personalization of cancer chronotherapy. Cancer Res 73(24):7176-88 |
| abstractText | 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-erbalpha 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-erbalpha and Bmal1 mRNA expressions and for irinotecan chronotoxicity in clock-altered Per2(m/m) mice. The application of a maximum-a-posteriori Bayesian inference method identified a linear model based on Rev-erbalpha and Bmal1 circadian expressions that accurately predicted for optimal irinotecan timing. The assessment of the Rev-erbalpha 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. |
