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靶向MDM2-p53相互作用用于乳腺癌治疗。

Targeting MDM2-p53 interaction for breast cancer therapy.

作者信息

Yousuf Amjad, Khan Najeeb Ullah

机构信息

Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taibah University, Madinah, 41477, Saudi Arabia.

Institute of Biotechnology and Genetic Engineering, The University of Agriculture, Peshawar, Peshawar, 25130, Pakistan.

出版信息

Oncol Res. 2025 Mar 19;33(4):851-861. doi: 10.32604/or.2025.058956. eCollection 2025.

Abstract

Breast cancer is a significant global concern, with limited effective treatment options. Therefore, therapies with high efficacy and low complications, unlike the existing chemotherapies, are urgently required. To address this issue, advances have been made in therapies targeting molecular pathways related to the murine double minute 2 proto-oncogene (MDM2)-tumor proteinp53 (TP53) interaction. This review aims to investigate the efficacy of MDM2 inhibition in restoring TP53 activity in breast cancer cells, as evidenced by clinical studies, reviews, and trials. TP53 is a tumor suppressor and MDM2 facilitates proteasomal degradation of TP53. MDM2 and TP53 activity is tightly regulated. However, cancerous breast cells overexpress through five hypothesized mechanisms. Consequently, TP53 levels decrease with increased tumor cell proliferation. Three strategies have been identified for controlling upregulation in cells with wild-type or mutated TP53. MDM2 inhibitors (MDM2i) are administered in combination with existing chemotherapies to reduce their effects on healthy cells. Few clinical and preclinical studies have been conducted using MDM2i, which necessitates high-quality clinical trials to support their therapeutic potential in breast cancer therapy.

摘要

乳腺癌是一个重大的全球关注问题,有效治疗选择有限。因此,与现有化疗不同,迫切需要高效且低并发症的治疗方法。为解决这一问题,针对与鼠双微体2原癌基因(MDM2)-肿瘤蛋白p53(TP53)相互作用相关分子途径的治疗已取得进展。本综述旨在通过临床研究、综述和试验来研究MDM2抑制在恢复乳腺癌细胞中TP53活性方面的疗效。TP53是一种肿瘤抑制因子,MDM2促进TP53的蛋白酶体降解。MDM2和TP53的活性受到严格调控。然而,乳腺癌细胞通过五种假设机制过度表达。因此,随着肿瘤细胞增殖增加,TP53水平降低。已确定三种策略来控制野生型或突变型TP53细胞中的MDM2上调。MDM2抑制剂(MDM2i)与现有化疗联合使用,以降低其对健康细胞的影响。使用MDM2i进行的临床和临床前研究很少,这需要高质量的临床试验来支持其在乳腺癌治疗中的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a4b3/11964874/292833d0f9e2/OncolRes-33-58956-f001.jpg

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