Predictive Medicine: Molecular Bases of Genetic Risk, Department of Experimental Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
Developmental Biology and Cancer Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, University College London, London, UK.
Nat Rev Urol. 2024 Mar;21(3):158-180. doi: 10.1038/s41585-023-00824-0. Epub 2023 Oct 17.
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.
近 50 年前，阿尔弗雷德·克努森（Alfred Knudson）提出肿瘤发生的“两次打击”模型，促使人们对维尔姆斯瘤（Wilms tumour）展开现代研究。此后，世界各地研究人员的努力大大扩展了我们对维尔姆斯瘤生物学的认识，包括遗传学方面的重大进展——从克隆第一个维尔姆斯瘤基因到揭示这种肿瘤遗传特征的高通量研究。这些发现增进了对维尔姆斯瘤胚胎起源、家族性发病和相关综合征情况的了解。人们已经做出许多努力来寻找和临床应用预测维尔姆斯瘤预后的生物标志物，因为该病的预后通常较好，但某些患者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，威尔姆斯瘤的临床前模型，从细胞系到类器官培养，也在不断发展。尽管取得了许多成就，但仍有许多有待发现：进一步深入了解维尔姆斯瘤的复发以及双侧维尔姆斯瘤的多种起源是两个正在积极研究的领域的例子。国际合作，特别是在需要获得稳健数据的大型肿瘤系列中进行合作，将有助于解答一些尚未解决的问题。
