昼夜节律和新型抗癌疗法的新选择

Uršula Prosenc Zmrzljak
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引用次数: 2

摘要

活动/睡眠、饮食/禁食等模式表明,我们的生活受到生物钟的控制。癌症是一种影响睡眠、饮食和新陈代谢的全身性疾病。所有这些过程一方面都受生物钟的调节,但另一方面,它们可以作为信号,通过强大的日常作息来收紧患者的生物钟。通常,抗癌治疗在医院进行,在那里病人的日常休息/活动模式被改变。然而,有研究表明,生物钟紊乱的肿瘤患者的生存结果较差。不同的抗癌疗法可以扰乱昼夜节律周期,但许多病例表明,肿瘤的昼夜节律本身是不受控制的。这一事实可用于规划抗癌治疗,使其在抗肿瘤方面最有效,但对周围健康组织的毒性最小。代谢过程受到高度调节,以防止能量浪费并确保足够的解毒;因此,外源代谢受到严格的昼夜节律控制。这为计划以时间调节的方式进行抗癌治疗提供了基本原理。我们回顾了一些潜在有用的抗癌治疗临床实践,并讨论了未来药物开发和设计中可能使用的不同方法。
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Circadian rhythms and new options for novel anticancer therapies
The patterns of activity/sleep, eating/fasting, etc show that our lives are under the control of an internal clock. Cancer is a systemic disease that affects sleep, feeding, and metabo- lism. All these processes are regulated by the circadian clock on the one hand, but on the other hand, they can serve as signals to tighten up the patient's circadian clock by robust daily routine. Usually, anticancer treatments take place in hospitals, where the patient's daily rest/activity pattern is changed. However, it has been shown that oncology patients with a disturbed circadian clock have poorer survival outcomes. The administration of different anticancer therapies can disturb the circadian cycle, but many cases show that circadian rhythms in tumors are deregulated per se. This fact can be used to plan anticancer therapies in such a manner that they will be most effective in antitumor action, but least toxic for the surrounding healthy tissue. Metabolic pro- cesses are highly regulated to prevent waste of energy and to ensure sufficient detoxification; as a consequence, xenobiotic metabolism is under tight circadian control. This gives the rationale for planning the administration of anticancer therapies in a chronomodulated manner. We review some of the potentially useful clinical praxes of anticancer therapies and discuss different pos- sible approaches to be used in drug development and design in the future.
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