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生物钟作为胰腺癌的潜在生物标志物和治疗靶点。

The circadian clock as a potential biomarker and therapeutic target in pancreatic cancer.

机构信息

Metabolic Syndrome Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

Transplant Research Center, Clinical Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran.

出版信息

Mol Cell Biochem. 2024 May;479(5):1243-1255. doi: 10.1007/s11010-023-04790-4. Epub 2023 Jul 5.

Abstract

Pancreatic cancer (PC) has a very high mortality rate globally. Despite ongoing efforts, its prognosis has not improved significantly over the last two decades. Thus, further approaches for optimizing treatment are required. Various biological processes oscillate in a circadian rhythm and are regulated by an endogenous clock. The machinery controlling the circadian cycle is tightly coupled with the cell cycle and can interact with tumor suppressor genes/oncogenes; and can therefore potentially influence cancer progression. Understanding the detailed interactions may lead to the discovery of prognostic and diagnostic biomarkers and new potential targets for treatment. Here, we explain how the circadian system relates to the cell cycle, cancer, and tumor suppressor genes/oncogenes. Furthermore, we propose that circadian clock genes may be potential biomarkers for some cancers and review the current advances in the treatment of PC by targeting the circadian clock. Despite efforts to diagnose pancreatic cancer early, it still remains a cancer with poor prognosis and high mortality rates. While studies have shown the role of molecular clock disruption in tumor initiation, development, and therapy resistance, the role of circadian genes in pancreatic cancer pathogenesis is not yet fully understood and further studies are required to better understand the potential of circadian genes as biomarkers and therapeutic targets.

摘要

胰腺癌(PC)在全球范围内具有非常高的死亡率。尽管一直在努力,但在过去的二十年中,其预后并没有显著改善。因此,需要进一步优化治疗方法。各种生物过程呈昼夜节律波动,并受内源性时钟调节。控制昼夜节律的机制与细胞周期紧密耦合,并能与肿瘤抑制基因/癌基因相互作用;因此,可能会影响癌症的进展。深入了解这些相互作用可能会发现预后和诊断生物标志物以及新的潜在治疗靶点。在这里,我们解释了生物钟系统如何与细胞周期、癌症以及肿瘤抑制基因/癌基因相关。此外,我们提出生物钟基因可能是某些癌症的潜在生物标志物,并综述了目前通过靶向生物钟治疗 PC 的最新进展。尽管早期诊断胰腺癌的努力取得了进展,但它仍然是一种预后不良和死亡率高的癌症。虽然研究表明分子钟破坏在肿瘤起始、发展和治疗耐药性中的作用,但生物钟基因在胰腺癌发病机制中的作用尚未完全阐明,需要进一步研究以更好地理解生物钟基因作为生物标志物和治疗靶点的潜力。

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