Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cancer Discov. 2024 Nov 1;14(11):2055-2060. doi: 10.1158/2159-8290.CD-24-0837.
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.
在药理学上靶向肿瘤抑制因子需要一种前所未有的策略，即恢复而不是常规抑制蛋白质功能，因此，p53 这种在癌症中最常见的突变蛋白仍然无法治疗。在这项研究中，我们解决了该领域长期存在的误解以及 p53 功能恢复策略的科学逻辑中的空白，确定了针对突变型 p53 药物研发的四个障碍，并相应地提出了有效性评估标准、临床转化规范以及突变型 p53 挽救化合物的前景。
