Department of Biology, University of Padova, I-35131, Italy.
Department of Biology, University of Padova, I-35131, Italy; Venetian Institute of Molecular Medicine, Via Orus 2, 35129 Padova, Italy.
Drug Discov Today. 2021 May;26(5):1164-1184. doi: 10.1016/j.drudis.2021.01.023. Epub 2021 Feb 4.
The circadian clock regulates a wide range of molecular pathways and biological processes. The expression of clock genes is often altered in cancer, fostering tumor initiation and progression. Inhibition and activation of core circadian clock genes, as well as treatments that restore circadian rhythmicity, have been successful in counteracting tumor growth in different experimental models. Here, we provide an up-to-date overview of studies that show the therapeutic effects of targeting the clock molecular machinery in cancer, both genetically and pharmacologically. We also highlight future areas for progress that offer a promising path towards innovative anticancer strategies. Substantial limitations in the current understanding of the complex interplay between the circadian clock and cancer in vivo need to be addressed in order to allow clock-targeting therapies in cancer.
生物钟调节着广泛的分子途径和生物过程。时钟基因的表达在癌症中经常发生改变，促进肿瘤的发生和发展。抑制和激活核心生物钟基因，以及恢复昼夜节律的治疗方法，在不同的实验模型中都成功地抑制了肿瘤生长。在这里，我们提供了一个最新的综述，展示了靶向时钟分子机制在癌症中的治疗效果，包括遗传和药理学方法。我们还强调了未来的进展领域，为创新的抗癌策略提供了有希望的途径。为了允许时钟靶向治疗在癌症中的应用，需要解决当前对生物钟与癌症体内复杂相互作用的理解中的实质性局限性。
