TP53, which encodes the tumour-suppressor protein p53, is the most frequently mutated gene across all cancer types. The presence of mutant p53 predisposes to cancer development, promotes the survival of cancer cells, and is associated with ineffective therapeutic responses and unfavourable prognoses. Despite these effects, no drug that abrogates the oncogenic functions of mutant p53 has yet been approved for the treatment of cancer. Current investigational therapeutic strategies are mostly aimed at restoring the wild-type activity of mutant p53, based on the assumption that all p53 mutants are functionally equal. Our increasing knowledge of mutant forms of p53, however, supports the antithetical hypothesis that not all p53 mutants have equivalent cellular effects; hence, a judicious approach to therapeutic targeting of mutant p53 is required. In this Review, we propose a categorization of the major classes of p53 mutants based on their functionality in tumour suppression and response to therapy. The emerging picture is that the mutations across TP53 form a 'rainbow of mutants', with varying degrees of functionality and different pathobiological consequences, necessitating the use of diverse therapeutic strategies to selectively target specific classes of mutation. The utility of this knowledge of TP53 mutations in developing selective therapeutic options, and in facilitating clinical decision-making is discussed.

TP53编码肿瘤抑制蛋白p53的，是所有癌症类型中最常见的突变基因。突变体p53的存在促进了癌症的发展，促进了癌细胞的存活，并与无效的治疗反应和不良的预后相关。尽管有这些作用，但尚无批准消除突变型p53致癌功能的药物用于癌症治疗。基于所有p53突变体在功能上相等的假设，当前的研究治疗策略主要旨在恢复突变体p53的野​​生型活性。然而，我们对p53突变体形式的了解不断增加，支持以下假说：并非所有p53突变体都具有同等的细胞效应。因此，需要一种明智的方法来治疗性靶向突变体p53。在这篇综述中，我们提出了基于p53突变体在肿瘤抑制和对治疗反应中的功能的主要分类。新兴的图景是TP53形成“突变体的彩虹”，具有不同程度的功能性和不同的病理生物学后果，因此有必要使用多种治疗策略来选择性地靶向特定类别的突变。讨论了这种TP53突变知识在开发选择性治疗方案和促进临床决策中的实用性。