title: The IGF signalling pathway in Wilms tumours--a report from  the ENCCA Renal Tumours Biology-driven drug development  workshop.
abstract: 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.
authors.forename: Mariana
authors.initials: M
authors.lastname: Maschietto
authors.forename: Jocelyn
authors.initials: J
authors.lastname: Charlton
authors.forename: Daniela
authors.initials: D
authors.lastname: Perotti
authors.forename: Paolo
authors.initials: P
authors.lastname: Radice
authors.forename: James I
authors.initials: JI
authors.lastname: Geller
authors.forename: Kathy
authors.initials: K
authors.lastname: Pritchard-Jones
authors.forename: Mark
authors.initials: M
authors.lastname: Weeks
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D035843:Biomedical Research; D015195:Drug Design; D044127:Epigenesis, Genetic; D016162:Genes, Wilms Tumor; D020022:Genetic Predisposition to Disease; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D058990:Molecular Targeted Therapy; D009154:Mutation; D010641:Phenotype; D017451:Receptors, Somatomedin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013002:Somatomedins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; D017451:Receptors, Somatomedin; D013002:Somatomedins