Division of Oncology, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Department of Neurology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Oncogene. 2021 May;40(18):3187-3200. doi: 10.1038/s41388-021-01778-6. Epub 2021 Apr 12.
Disruption of the cellular pathway modulating endogenous 24-h rhythms, referred to as "the circadian clock", has been recently proven to be associated with cancer risk, development, and progression. This pathway operates through a complex network of transcription-translation feedback loops generated by a set of interplaying proteins. The expression of core circadian clock genes is frequently dysregulated in human tumors; however, the specific effects and underlying mechanisms seem to vary depending on the cancer types and are not fully understood. In addition, specific oncogenes may differentially induce the dysregulation of the circadian clock in tumors. Pharmacological modulation of clock components has been shown to result in specific lethality in certain types of cancer cells, and thus holds great promise as a novel anti-cancer therapeutic approach. Here we present an overview of the rationale and current evidence for targeting the clock in cancer treatment.
破坏调节内源性 24 小时节律的细胞通路，即“生物钟”，最近已被证明与癌症风险、发展和进展有关。该通路通过一组相互作用的蛋白质产生的转录-翻译反馈环的复杂网络运作。核心生物钟基因的表达在人类肿瘤中经常失调；然而，具体的影响和潜在的机制似乎因癌症类型而异，目前还不完全清楚。此外，特定的癌基因可能会以不同的方式诱导肿瘤中生物钟的失调。时钟成分的药理学调节已被证明可导致某些类型的癌细胞特异性死亡，因此作为一种新的抗癌治疗方法具有很大的前景。在这里，我们概述了靶向癌症治疗时钟的基本原理和现有证据。
