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p53 再激活在宫颈癌治疗中的潜力。

Therapeutic potential of p53 reactivation in cervical cancer.

机构信息

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, 110004, LN, China.

Department of Radiology, Shengjing Hospital of China Medical University, Shenyang, 110004, LN, China.

出版信息

Crit Rev Oncol Hematol. 2021 Jan;157:103182. doi: 10.1016/j.critrevonc.2020.103182. Epub 2020 Nov 24.

Abstract

Cervical cancer (CC) is one of most common malignancies affecting women worldwide. To date, surgical resection is the only effective radical remedy for CC at its early stages, while the prognosis of metastatic or recurrent CC is very poor. Dysfunction of the tumor suppressor p53 due to aberrant expression, post-translational modification, mutations, SNPs, and LOH as well as sequestration by viral antigens and MDM2/HDM2-mediated degradation is closely associated with the therapeutic insensitivity and relapse of many malignancies, including CC. Accumulating studies have demonstrated that restoration of p53 activity can induce cell cycle arrest and apoptosis, eliminate radio- and chemotherapy resistance, and inhibit tumor growth in CC cells. Therefore, activation of wild-type p53 as well as restoration of p53 function seems appealing as a therapeutic strategy. In this review, we focus on the potential roles of p53 reactivation in CC treatment and their underlying molecular mechanisms towards the development of novel therapies.

摘要

宫颈癌(CC)是全球范围内影响女性的最常见恶性肿瘤之一。迄今为止,手术切除是 CC 早期唯一有效的根治方法,而转移性或复发性 CC 的预后非常差。由于异常表达、翻译后修饰、突变、单核苷酸多态性和杂合性缺失以及病毒抗原的隔离和 MDM2/HDM2 介导的降解,肿瘤抑制因子 p53 的功能障碍与许多恶性肿瘤(包括 CC)的治疗不敏感和复发密切相关。越来越多的研究表明,恢复 p53 活性可以诱导细胞周期停滞和细胞凋亡,消除放射和化学疗法耐药性,并抑制 CC 细胞中的肿瘤生长。因此,激活野生型 p53 以及恢复 p53 功能似乎是一种有吸引力的治疗策略。在这篇综述中,我们重点介绍了 p53 再激活在 CC 治疗中的潜在作用及其潜在的分子机制,以期开发新的治疗方法。

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