The IGF signalling pathway in Wilms tumours - A report from the ENCCA Renal Tumours Biology-driven drug development workshop

Mariana Maschietto, Jocelyn Charlton, Daniela Perotti, Paolo Radice, James I. Geller, Kathy Pritchard-Jones and Mark Weeks _

PDF  |  HTML  |  How to cite

Oncotarget. 2014; 5:8014-8026. https://doi.org/10.18632/oncotarget.2485

Metrics: PDF 2379 views  |   HTML 3354 views  |   ?  


Mariana Maschietto1,*, Jocelyn Charlton1,*, Daniela Perotti2, Paolo Radice2, James I. Geller3, Kathy Pritchard-Jones1 and Mark Weeks1

1 Cancer Section, Institute of Child Health, University College London, London WC1N 1EH, UK

2 Molecular Bases of Genetic Risk and Genetic Testing Unit, Department of Preventive and Predictive Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

3 UC department of paediatrics, Cincinnati Children’s Hospital, Cincinnati, Ohio, USA

* These authors contributed equally to this work


Mark Weeks, email:

Keywords: IGF2, IGF signalling pathway, Wilms tumour, targeted therapy, DNA methylation

Received: August 11, 2014 Accepted: September 15, 2014 Published: September 16, 2014


It is hypothesised that Wilms tumour (WT) results from aberrant renal development due to its embryonic morphology, associated undifferentiated precursor lesions (termed nephrogenic rests) and embryonic kidney-like chromatin and gene expression profiles. From the study of overgrowth syndrome-associated WT, germline dysregulation was identified in the imprinted region at 11p15 affecting imprinted genes IGF2 and H19. This is also detected in ~70% sporadic cases, making this the most common somatic molecular aberration in WT. This review summarises the critical discussion at an international workshop held under the auspices of The European Network for Cancer Research in Children and Adolescents (ENCCA) consortium, where the potential for drug development to target IGF2 and the WT epigenome was debated. Here, we consider current cancer treatments which include targeting the IGF pathway and the use of methylation agents alone or in combination with other drugs in clinical trials of paediatric cancers. Finally, we discuss the possibility of the use of these drugs to treat patients with WT.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.
PII: 2485