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p21 在癌症放射治疗中的多重作用。

Multiple functions of p21 in cancer radiotherapy.

机构信息

Institute of Modern Physics, Chinese Academy of Sciences, 509 Nanchang Road, Lanzhou, 730000, Gansu, China.

Key Laboratory of Heavy Ion Radiation Biology and Medicine, Chinese Academy of Sciences, Lanzhou, 730000, China.

出版信息

J Cancer Res Clin Oncol. 2021 Apr;147(4):987-1006. doi: 10.1007/s00432-021-03529-2. Epub 2021 Feb 5.

Abstract

BACKGROUND

Greater than half of cancer patients experience radiation therapy, for both radical and palliative objectives. It is well known that researches on radiation response mechanisms are conducive to improve the efficacy of cancer radiotherapy. p21 was initially identified as a widespread inhibitor of cyclin-dependent kinases, transcriptionally modulated by p53 and a marker of cellular senescence. It was once considered that p21 acts as a tumour suppressor mainly to restrain cell cycle progression, thereby resulting in growth suppression. With the deepening researches on p21, p21 has been found to regulate radiation responses via participating in multiple cellular processes, including cell cycle arrest, apoptosis, DNA repair, senescence and autophagy. Hence, a comprehensive summary of the p21's functions in radiation response will provide a new perspective for radiotherapy against cancer.

METHODS

We summarize the recent pertinent literature from various electronic databases, including PubMed and analyzed several datasets from Gene Expression Omnibus database. This review discusses how p21 influences the effect of cancer radiotherapy via involving in multiple signaling pathways and expounds the feasibility, barrier and risks of using p21 as a biomarker as well as a therapeutic target of radiotherapy.

CONCLUSION

p21's complicated and important functions in cancer radiotherapy make it a promising therapeutic target. Besides, more thorough insights of p21 are needed to make it a safe therapeutic target.

摘要

背景

超过一半的癌症患者接受放射治疗,无论是根治性还是姑息性的。众所周知,对放射反应机制的研究有助于提高癌症放射治疗的疗效。p21 最初被鉴定为细胞周期蛋白依赖性激酶的广泛抑制剂,受 p53 转录调节,是细胞衰老的标志物。曾经认为,p21 主要作为肿瘤抑制因子发挥作用,通过抑制细胞周期进程来抑制细胞生长。随着对 p21 的深入研究,发现 p21 通过参与多个细胞过程(包括细胞周期阻滞、细胞凋亡、DNA 修复、衰老和自噬)来调节放射反应。因此,对 p21 在放射反应中的作用进行全面总结,将为癌症放射治疗提供新的视角。

方法

我们从包括 PubMed 在内的多个电子数据库中总结了最近的相关文献,并分析了来自基因表达综合数据库的几个数据集。本综述讨论了 p21 如何通过参与多个信号通路影响癌症放射治疗的效果,并阐述了将 p21 作为放射治疗的生物标志物和治疗靶点的可行性、障碍和风险。

结论

p21 在癌症放射治疗中的复杂而重要的功能使其成为一个有前途的治疗靶点。此外,需要更深入地了解 p21,使其成为一个安全的治疗靶点。

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