p53靶向药物开发的基础和新兴前沿
Fundamentals and emerging frontiers in p53-targeted drug development.
摘要(中文译文)
作为关键的抑癌蛋白，p53在细胞周期调控、DNA修复、细胞凋亡和代谢等生物学过程中发挥核心作用。然而，p53基因突变或功能失活在超过50%的人类癌症中普遍存在，导致肿瘤发生、发展及耐药，使其成为抗肿瘤药物研发的重要靶点。目前，靶向p53的治疗面临突变类型多样、药物特异性不足及耐药性等挑战。本文系统综述了靶向p53药物研发的基础理论与前沿进展。阐述了p53的结构与功能及其突变致癌机制，继而重点分析了小分子药物（如APR-246）的研究历程与临床转化现状，探讨了基因治疗与免疫治疗策略的应用前景，并介绍了基于CRISPR和PROTAC技术的新兴疗法。通过整合最新研究成果，本文旨在为靶向p53药物的精准研发与临床转化提供理论依据和方向性指导。
Abstract
As a key tumor suppressor protein, p53 plays a central role in biological processes such as cell cycle regulation, DNA repair, apoptosis, and metabolism. However, p53 gene mutations or functional inactivation are prevalent in over 50% of human cancers, leading to tumorigenesis, development, and drug resistance, making it an important target for anticancer drug development. Currently, p53-targeted therapy faces challenges such as diverse mutation types, insufficient drug specificity, and drug resistance. This article systematically reviews the fundamental theories and cutting-edge advances in the development of p53-targeted drugs. It elaborates on the structure and function of p53 and its mutation-induced carcinogenic mechanisms, then focuses on analyzing the research history and clinical translation status of small-molecule drugs (e.g., APR-246), discusses the application prospects of gene therapy and immunotherapy strategies, and introduces emerging therapies based on CRISPR and PROTAC technologies. By integrating the latest research findings, this article aims to provide theoretical basis and directional guidance for the precise development and clinical translation of p53-targeted drugs.
如何引用
AMA
Hui-Deng Long, Ning Zhang, Wen-Er Wang, Yu-Shui Ma, Fu-Xing Liu, Zi-Yu Chen, et al. Fundamentals and emerging frontiers in p53-targeted drug development.. Biochemistry and biophysics reports. 2026; doi:10.1016/j.bbrep.2026.102661.
APA
Hui-Deng Long, Ning Zhang, Wen-Er Wang, Yu-Shui Ma, Fu-Xing Liu, Zi-Yu Chen, et al (2026). Fundamentals and emerging frontiers in p53-targeted drug development.. Biochemistry and biophysics reports. https://doi.org/10.1016/j.bbrep.2026.102661
GB/T 7714
Hui-Deng Long, Ning Zhang, Wen-Er Wang, Yu-Shui Ma, Fu-Xing Liu, Zi-Yu Chen, et al. Fundamentals and emerging frontiers in p53-targeted drug development.[J]. Biochemistry and biophysics reports, 2026 doi:10.1016/j.bbrep.2026.102661.
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