Project

Unraveling the molecular mechanisms driving the formation of Wilms tumor through novel genetic models and cross-species multi-omics analyses

Code
11A4E25N
Duration
01 November 2024 → 14 November 2028
Funding
Research Foundation - Flanders (FWO)
Research disciplines
  • Medical and health sciences
    • Cancer biology
    • Cancer therapy
    • Oncology not elsewhere classified
Keywords
Genetic cancer models Multiomics CRISPR multiplexing
 
Project description

Wilms tumor, a malignant kidney cancer commonly found in infants and young children, can have a survival rate of over 90% with current treatments. However, around 20% of patients experience relapse after initial treatment, and up to 25% of Wilms tumor survivors may suffer from severe chronic side effects. Furthermore, some subtypes of Wilms tumor have a less favorable prognosis, making it crucial to identify more targeted treatment approaches. However, there are only a limited number of animal models available, hindering our understanding of these tumors. Therefore, the goal of this research project is to develop new models for clinically identified Wilms tumor subtypes using Xenopus tropicalis, an organism in which genetic modification via CRISPR technologies is easily and efficiently applicable. By thoroughly examining gene expression and the epigenetic state of the genome in these models and comparing them with mouse models and human organoids, we aim to identify new vulnerabilites for subtype specific Wilms tumor. A previouisly established pipeline for CRISPR mediated dependency mapping is used to assess possible critical genetic vulnerabilities in these tumors. The ultimate aim of this project is to utilize the insights gained to uncover advanced, more precise treatments, thereby enhancing patient care and diminishing the likelihood of enduring complications.