Summary: Pharmacologically targeting tumor suppressors necessitates an unprecedented strategy of restoring, rather than conventionally inhibiting, protein function, and p53, the most commonly mutated protein in cancer, has thus remained undruggable. In this study, we address long-standing misconceptions in the field and gaps in the scientific logic for a p53 function–restoration strategy, identify four barriers for drugging mutant p53, and accordingly propose effectiveness evaluation criteria, clinical-translating norms, and prospects for mutant p53 rescue compounds.

中文翻译：

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药物 p53：障碍、标准和前景


摘要： 药理学靶向肿瘤抑制因子需要一种前所未有的策略来恢复蛋白质功能，而不是常规抑制蛋白质功能，因此 p53 是癌症中最常见的突变蛋白，因此仍然不可成药。在这项研究中，我们解决了该领域长期存在的误解和 p53 功能恢复策略科学逻辑中的空白，确定了突变体 p53 药物的四个障碍，并相应地提出了突变 p53 拯救化合物的有效性评估标准、临床转化规范和前景。