Szabova L , et al., Perturbation of Rb, P53 and Brca1 or Brca2 Cooperate in Inducing Metastatic Serous Epithelial Ovarian Cancer. Cancer Res, 2012.
Metabolonresults led to:
- Biomarkers from a preclinical model that translate to human
- A new paradigm for matching preclinical models to human tumor types, improving translational potential for drug R&D
- Metabolites observed in mouse plasma that were also in human tumor tissue
Ovarian cancer is a leading cause of cancer death in women. High grade serous epithelial ovarian cancer (SEOC) is a particularly aggressive form and effective therapeutic targeting requires meaningful tumor models. Preclinical models that recapitulate the complexity of a human tumor are largely considered inadequate and are a major limitation in translating promising preclinical results to clinical success. To derive a more faithful tumor model, investigators were able to blend common mutations in SEOC into GEM mouse models and used gene expression and metabolomicsignatures to qualify the model in relation to the human tumor characteristics. Further validating the GEM model was a panel of blood metabolites from the mouse that exhibited a similar pattern to human tumors. This study provides a roadmap for how to leverage cancer genetics and metabolomicsto ensure the greatest potential for translatability.