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. 2021 Oct 7;53(10):1529–1538. doi: 10.1038/s12276-021-00681-0

Fig. 5. Circadian timing of cancer medicine.

Fig. 5

The purpose of chronotherapy in anticancer medicine is to improve host tolerance and safety (a) or tumor cytotoxicity (b). a Chronotissue tolerance in anticancer therapy. The antiphasic peak and trough levels of dihydropyrimidine dehydrogenase (DPD), an elimination enzyme of 5-FU, and thymidine synthase (TS) in host tissues are associated with reduced toxicity with 5-FU treatment. Daily variation in the levels of glutathione (GSH), a potent antioxidant, is another host chronotolerance biomarker to consider when platinum-based anticancer drugs (e.g., oxaliplatin and cisplatin) are used. For example, doxorubicin is more effective and causes fewer side effects with morning treatment. b Chronotumor toxicity of antitumor agents. Daily rhythms in the tumor-specific cell cycle can be targeted by various cell cycle-specific anticancer drugs, including those that target the G1 phase (seliciclib), G–S phase transition (palbociclib), S phase (5-FU), and M phase (docetaxel). G; cell growth, S; DNA synthesis, M; mitosis. c Circadian regulation of the time-of-day specificity of antitumor drugs. Circadian clock function in tumors regulates cell cycle rhythms that mediate the dose-time-dependent cytotoxicity of antitumor drugs. Genetic ablation of BMAL1 (BMAL1 KO; dashed line) in tumors abolishes cell cycle rhythms and the time-of-day-specific drug sensitivity present in intact tumor cells (BMAL1 WT; solid line).