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Circadian Clock, Cancer, and Chemotherapy

机译：昼夜节律时钟，癌症和化学疗法

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The circadian clock is a global regulatory system that interfaces with most other regulatory systems and pathways in mammalian organisms. Investigations of the circadian clockDNA damage response connections have revealed that nucleotide excision repair, DNA damage checkpoints, and apoptosis are appreciably influenced by the clock. Although several epidemiological studies in humans and a limited number of genetic studies in mouse model systems have indicated that clock disruption may predispose mammals to cancer, well-controlled genetic studies in mice have not supported the commonly held view that circadian clock disruption is a cancer risk factor. In fact, in the appropriate genetic background, clock disruption may instead aid in cancer regression by promoting intrinsic and extrinsic apoptosis. Finally, the clock may affect the efficacy of cancer treatment (chronochemotherapy) by modulating the pharmacokinetics and pharmacodynamics of chemotherapeutic drugs as well as the activity of the DNA repair enzymes that repair the DNA damage caused by anticancer drugs.
机译：昼夜节律时钟是一个全球性的调节系统，可与哺乳动物有机体中的大多数其他调节系统和途径相接。对昼夜节律时钟DNA损伤反应联系的研究表明，核苷酸切除修复，DNA损伤检查点和细胞凋亡受时钟的影响很大。尽管对人体进行的几项流行病学研究和对小鼠模型系统的基因研究数量有限，但这些研究表明时钟干扰可能使哺乳动物易患癌症，但对小鼠进行良好控制的基因研究并不能普遍支持昼夜节律干扰是患癌症的风险。因子。实际上，在适当的遗传背景下，时钟破坏可能会通过促进内在和外在的细胞凋亡来帮助癌症消退。最后，时钟可能会通过调节化学治疗药物的药代动力学和药效学以及修复由抗癌药引起的DNA损伤的DNA修复酶的活性来影响癌症治疗（计时疗法）的功效。

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