The p53 transcription factor was first described over three decades ago and is one of the most studied proteins, with over 60,000 PubMed listed publications. Despite being first described as an oncogene, p53 has long been recognized as a major tumor suppressor and the most commonly mutated gene in human cancer. The frequent inactivation of p53 in tumors fostered the attractive notion that its functional reinstatement would constitute an effective tumor-specific therapy. Strategies aimed at restoring wild-type p53 function in tumors are being actively pursued and some have reached clinical trials, highlighting the important translational potential of this new field of research. The therapeutic impact of those strategies in human cancer was recently modeled in mice where a clear, even if limited, therapeutic benefit of p53-targeted therapies was established. As unexpected aspects of p53 tumor suppressive function continue to be uncovered, new opportunities arise to further improve p53 therapy outcome. In this review we discuss the in vivo mechanisms underlying p53-mediated tumor prevention, the impact of p53 functional restoration in tumors and how this knowledge may be exploited to improve the efficacy of p53-targeted cancer therapy. A particular emphasis is given to the newly identified metabolic functions of p53.

中文翻译：

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从肿瘤预防到治疗：赋予 p53 反击的能力。

p53 转录因子在 30 多年前首次被描述，是研究最多的蛋白质之一，有超过 60,000 篇 PubMed 列出的出版物。尽管 p53 最初被描述为一种癌基因，但长期以来一直被认为是一种主要的肿瘤抑制基因，也是人类癌症中最常见的突变基因。肿瘤中 p53 的频繁失活引发了一个有吸引力的观点，即其功能恢复将构成有效的肿瘤特异性治疗。旨在恢复肿瘤中野生型 p53 功能的策略正在积极推行，其中一些已进入临床试验，突出了这一新研究领域的重要转化潜力。这些策略对人类癌症的治疗影响最近在小鼠身上进行了建模，其中明确的，即使是有限的，确定了 p53 靶向治疗的治疗益处。随着 p53 肿瘤抑制功能的意外方面不断被发现，出现了进一步改善 p53 治疗结果的新机会。在这篇综述中，我们讨论了 p53 介导的肿瘤预防的体内机制、p53 功能恢复对肿瘤的影响以及如何利用这些知识来提高 p53 靶向癌症治疗的功效。特别强调了新发现的 p53 代谢功能。p53 功能恢复在肿瘤中的影响以及如何利用这一知识来提高 p53 靶向癌症治疗的功效。特别强调了新发现的 p53 代谢功能。p53 功能恢复在肿瘤中的影响以及如何利用这一知识来提高 p53 靶向癌症治疗的功效。特别强调了新发现的 p53 代谢功能。