近 50 年前，阿尔弗雷德·克努森 (Alfred Knudson) 提出了肿瘤发展的“两次打击”模型，由此引发了对肾母细胞瘤的现代研究。从那时起，世界各地研究人员的努力极大地扩展了我们对肾母细胞瘤生物学的了解，包括遗传学方面的重大进展 - 从克隆第一个肾母细胞瘤基因到揭示该肿瘤遗传图谱的高通量研究。这些发现增进了对肾母细胞瘤胚胎起源、家族发生和相关综合征的了解。人们已经做出了许多努力来寻找肾母细胞瘤的预后生物标志物并将其应用于临床，其结果通常是有利的，但对一些受影响个体的治疗仍然具有挑战性。生物标志物的肿瘤内异质性也带来了挑战。此外，肾母细胞瘤的临床前模型，从细胞系到类器官培养物，已经不断发展。尽管取得了这些成就，仍有许多工作有待发现：对肾母细胞瘤复发和双侧肾母细胞瘤的多重起源的进一步分子理解是正在积极研究领域的两个例子。国际合作，特别是当需要大型肿瘤系列以获得可靠数据时，将有助于回答一些尚未解决的问题。© 2023。施普林格自然有限公司。

The modern study of Wilms tumour was prompted nearly 50 years ago, when Alfred Knudson proposed the 'two-hit' model of tumour development. Since then, the efforts of researchers worldwide have substantially expanded our knowledge of Wilms tumour biology, including major advances in genetics - from cloning the first Wilms tumour gene to high-throughput studies that have revealed the genetic landscape of this tumour. These discoveries improve understanding of the embryonal origin of Wilms tumour, familial occurrences and associated syndromic conditions. Many efforts have been made to find and clinically apply prognostic biomarkers to Wilms tumour, for which outcomes are generally favourable, but treatment of some affected individuals remains challenging. Challenges are also posed by the intratumoural heterogeneity of biomarkers. Furthermore, preclinical models of Wilms tumour, from cell lines to organoid cultures, have evolved. Despite these many achievements, much still remains to be discovered: further molecular understanding of relapse in Wilms tumour and of the multiple origins of bilateral Wilms tumour are two examples of areas under active investigation. International collaboration, especially when large tumour series are required to obtain robust data, will help to answer some of the remaining unresolved questions.© 2023. Springer Nature Limited.