p53 基因的突变损害了其作为基因组完整性守护者的作用，主要产生错义 p53 突变蛋白。功能获得假说长期以来表明这些突变蛋白获得了新的致癌特性。然而，最近的研究挑战了这一观点，表明针对这些突变体可能不会影响癌细胞的适应性。越来越多的证据表明，肿瘤发生涉及驱动突变和细胞状态之间的相互作用，并受到发育阶段、外部损伤和组织损伤的影响。一致地，p53 突变体的行为和特性会因环境而改变。本文旨在对有关 p53 突变体在癌症生物学中的贡献的不断变化的证据提供平衡的总结，同时考虑替代框架来破译 p53 突变体在其生理背景下的复杂性。版权所有 © 2024 作者。由爱思唯尔有限公司出版。保留所有权利。

Mutations in the p53 gene compromise its role as guardian of genomic integrity, yielding predominantly missense p53 mutant proteins. The gain-of-function hypothesis has long suggested that these mutant proteins acquire new oncogenic properties; however, recent studies challenge this notion, indicating that targeting these mutants may not impact the fitness of cancer cells. Mounting evidence indicates that tumorigenesis involves a cooperative interplay between driver mutations and cellular state, influenced by developmental stage, external insults, and tissue damage. Consistently, the behavior and properties of p53 mutants are altered by the context. This article aims to provide a balanced summary of the evolving evidence regarding the contribution of p53 mutants in the biology of cancer while contemplating alternative frameworks to decipher the complexity of p53 mutants within their physiological contexts.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.