Li–Fraumeni syndrome (LFS) is a rare hereditary autosomal dominant cancer disorder. Germline mutations in TP53, the gene encoding p53, are responsible for most cases of LFS. TP53 is also the most commonly mutated gene in human cancers. Because inhibition of mutant p53 is considered to be a promising therapeutic strategy to treat these diseases, LFS provides a perfect genetic model to study p53 mutation-associated malignancies as well as to screen potential compounds targeting oncogenic p53. In this review we briefly summarize the biology of LFS and current understanding of the oncogenic functions of mutant p53 in cancer development. We discuss the strengths and limitations of current LFS disease models, and touch on existing compounds targeting oncogenic p53 and in vitro clinical trials to develop new ones. Finally, we discuss how recently developed methodologies can be integrated into the LFS induced pluripotent stem cell (iPSC) platform to develop precision cancer therapy.

Li-Fraumeni综合征（LFS）是一种罕见的遗传性常染色体显性遗传癌症疾病。TP53（编码p53的基因）中的种系突变是大多数LFS的原因。TP53也是人类癌症中最常见的突变基因。因为抑制突变体p53被认为是治疗这些疾病的一种有前途的治疗策略，所以LFS提供了一个完美的遗传模型来研究与p53突变相关的恶性肿瘤，并筛选靶向致癌性p53的潜在化合物。在这篇综述中，我们简要总结了LFS的生物学特性以及当前对突变p53在癌症发展中的致癌功能的了解。我们讨论了当前LFS疾病模型的优势和局限性，并探讨了针对致癌性p53和体外的现有化合物开发新的临床试验。最后，我们讨论如何将最近开发的方法集成到LFS诱导的多能干细胞（iPSC）平台中，以开发精确的癌症治疗方法。