p53/MDM2 signaling pathway in aging, senescence and tumorigenesis.

IF 12.1 1区医学 Q1 ONCOLOGY

Seminars in cancer biology Pub Date : 2024-05-17 DOI:10.1016/j.semcancer.2024.05.001

Youyi Huang, Xiaofang Che, Peter W Wang, Xiujuan Qu

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引用次数: 0

Abstract

A wealth of evidence has emerged that there is an association between aging, senescence and tumorigenesis. Senescence, a biological process by which cells cease to divide and enter a status of permanent cell cycle arrest, contributes to aging and aging-related diseases, including cancer. Aging populations have the higher incidence of cancer due to a lifetime of exposure to cancer-causing agents, reduction of repairing DNA damage, accumulated genetic mutations, and decreased immune system efficiency. Cancer patients undergoing cytotoxic therapies, such as chemotherapy and radiotherapy, accelerate aging. There is growing evidence that p53/MDM2 (murine double minute 2) axis is critically involved in regulation of aging, senescence and oncogenesis. Therefore, in this review, we describe the functions and mechanisms of p53/MDM2-mediated senescence, aging and carcinogenesis. Moreover, we highlight the small molecular inhibitors, natural compounds and PROTACs (proteolysis targeting chimeras) that target p53/MDM2 pathway to influence aging and cancer. Modification of p53/MDM2 could be a potential strategy for treatment of aging, senescence and tumorigenesis.

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p53/MDM2 信号通路在衰老、衰老和肿瘤发生中的作用。

大量证据表明，衰老、衰老和肿瘤发生之间存在关联。衰老是细胞停止分裂并进入永久性细胞周期停滞状态的一种生物过程，是导致衰老和与衰老相关的疾病（包括癌症）的原因之一。由于终生暴露于致癌物质、DNA 损伤修复能力下降、基因突变累积以及免疫系统效率降低，老龄人口的癌症发病率较高。接受化疗和放疗等细胞毒疗法的癌症患者会加速衰老。越来越多的证据表明，p53/MDM2（鼠双分 2）轴在衰老、衰老和肿瘤发生的调控过程中起着至关重要的作用。因此，在这篇综述中，我们描述了 p53/MDM2 介导的衰老、老化和癌变的功能和机制。此外，我们还重点介绍了针对 p53/MDM2 通路影响衰老和癌症的小分子抑制剂、天然化合物和 PROTACs（蛋白水解靶向嵌合体）。改变 p53/MDM2 可能是治疗衰老、衰老和肿瘤发生的一种潜在策略。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Seminars in cancer biology 医学-肿瘤学

CiteScore

26.80

自引率

4.10%

发文量

347

审稿时长

15.1 weeks

期刊介绍： Seminars in Cancer Biology (YSCBI) is a specialized review journal that focuses on the field of molecular oncology. Its primary objective is to keep scientists up-to-date with the latest developments in this field. The journal adopts a thematic approach, dedicating each issue to an important topic of interest to cancer biologists. These topics cover a range of research areas, including the underlying genetic and molecular causes of cellular transformation and cancer, as well as the molecular basis of potential therapies. To ensure the highest quality and expertise, every issue is supervised by a guest editor or editors who are internationally recognized experts in the respective field. Each issue features approximately eight to twelve authoritative invited reviews that cover various aspects of the chosen subject area. The ultimate goal of each issue of YSCBI is to offer a cohesive, easily comprehensible, and engaging overview of the selected topic. The journal strives to provide scientists with a coordinated and lively examination of the latest developments in the field of molecular oncology.