Serious Epithelial Ovarian Cancer

Genetically engineered mouse model

• Developed in house
• Genetic aberrations:
  • Inactivation of Rb tumor suppression (via K18-T121 transgene)
  • Tp53 loss or mutation (R172H)
  • Brca1 or Brca2 loss
• Induction by injection of adenovirus expressing Cre recombinase under the ovrian bursa
• Pathology:
  • Serious epithelial ovarian cancer (SEOC)
  • Peritoneal carcinomatosis
  • Distal metastases (lung, liver)
  • Ascites
• Latency: 8-12 months (high grade tumor)
• Metabolomic and geme expression profile aligns with human SEOC
• Szabova et al., Pertubation of Rb, p53 and Brca1 or Brca2 cooperate in inducing metastatic serous epithelial ovarian cancer (Cancer Res 2012)

Orthotopic allograft model

• Derived from genetically engineered mouse ovarian tumors
• Ovarian tumor transplant to wild-type recipient mice
• Genetic aberrations:
  • Inactivation of Rb tumor suppression (via K18-T121 transgene)
  • Tp53 loss or mutatiuon (R172H)
  • Bra1 or Brca2 loss
• Pathology:
  • Serous epithelial ovarian cancer (SEOC)
  • Peritoneal carcinomatosis
  • Distal metastases (lung, liver)
  • Ascites
• Latency: 1-3 months
• Molecular profile aligns with human SEOC
• Ultrasound imaging
• Differential response to therapeutics in Brca1 deficient vs Brca1 wild type tumors
• Szabova et al., Pathway-specific engineered mouse allograft models functionally recapitulate human serous epithelial ovarian cancer (PloS One 2014)