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活性氧诱导的细胞周期停滞作为多非整倍体癌细胞(PACC)耐药的一种机制。

ROS-induced cell cycle arrest as a mechanism of resistance in polyaneuploid cancer cells (PACCs).

机构信息

James Buchanan Brady Urological Institute at the Johns Hopkins School of Medicine (600 North Wolfe Street, Baltimore, MD, 21287, United States.

James Buchanan Brady Urological Institute at the Johns Hopkins School of Medicine (600 North Wolfe Street, Baltimore, MD, 21287, United States.

出版信息

Prog Biophys Mol Biol. 2021 Oct;165:3-7. doi: 10.1016/j.pbiomolbio.2021.05.002. Epub 2021 May 12.

Abstract

Cancer is responsible for the deaths of millions of people worldwide each year. Once metastasized, the disease is incurable and shows resistance to all anti-cancer therapies. The already-elevated level of reactive oxygen species (ROS) in cancer cells is further increased by therapies. The oxidative stress activates the DNA damage response (DDR) and the stressed cancer cell moves towards cell cycle arrest. Once arrested, the majority of cancer cells will undergo programmed cell death in the form of apoptosis. If the cancer cell is able to exit the cell cycle prior to cell division and enter a protected G0 state, it is able to withstand and survive therapy as a polyaneuploid cancer cell (PACC) and eventually seed resistant tumor growth.

摘要

癌症每年导致全球数百万人死亡。一旦转移,这种疾病是无法治愈的,并对所有抗癌疗法表现出耐药性。治疗方法进一步增加了癌细胞中已经升高的活性氧(ROS)水平。氧化应激激活了 DNA 损伤反应(DDR),应激的癌细胞会进入细胞周期停滞。一旦停滞,大多数癌细胞将以细胞凋亡的形式进行程序性细胞死亡。如果癌细胞能够在细胞分裂之前退出细胞周期并进入受保护的 G0 状态,它就能够作为多倍体癌细胞(PACC)耐受并存活治疗,并最终引发耐药性肿瘤生长。

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