Poster Presentation 27th Lorne Cancer Conference 2015

Exploring targeted therapies for high-grade epithelial ovarian cancer utilising a novel patient-derived xenograft. (#332)

Gwo Yaw Ho 1 , M Topp 1 , A Hadley 1 , V Heong 1 , P Pollock 2 , ML Labat 1 , O McNally 3 , Australian Ovarian Cancer Study (AOCS) 4 , S Fox 4 , D Bowtell 4 , MJ Wakefield 1 , CL Scott 1
  1. Walter and Eliza Hall Institute, Doncaster, VIC, Australia
  2. Translational Research Institute, Brisbane, QLD, Australia
  3. Royal Women’s Hospital, Melbourne, VIC, Australia
  4. Peter MacCallum Cancer Centre, Melbourne, VIC, Australia

Introduction: The poor survival outcome of patients with high-grade epithelial ovarian cancer (HG-EOC) has not changed during the last three decades despite multiple large phase III studies involving the use of combination chemotherapeutic agents and anti-angiogenic therapies. This is largely owing to the tremendous heterogeneity of ovarian cancer. The current “one size fits all” traditional treatment approach is not effective. We are using molecular and functional characterization of patient-derived xenografts (PDX) to prioritise therapies, including for a rare HG-EOC PDX with documented Fibroblast Growth Factor Receptor 3 (FGFR3) amplification.

Method: Fresh HG-EOC tumour was obtained at the time of surgery during first patient relapse and was transplanted subcutaneously into NOD-SCID-IL2Rγnull mice. The resultant PDX was passaged via the intra-peritoneal route, to generate both solid tumour and ascites. An adherent cell line was generated from the ascites. A second patient biopsy sample was received following progression after second-line chemotherapy, which is being observed. Molecular characterization and in vitro and in vivo response to standard therapy with cisplatin and to novel therapeutics is being performed.

Results: Preliminary assessment of in vivo cisplatin response revealed initial tumour regression followed by relapse (n = 3 mice per arm), consistent with the patient’s response to platinum-based chemotherapy. The subsequent patient (biopsy) sample was noted by Foundation Medicine testing to contain amplification of FGFR3, MITF and ASLX2 and no defect in DNA repair pathways was identified. Cell line proliferation is being assessed using the Cell Titre Glo method for relevant therapeutics.

Conclusion: From this rare FGFR3-amplified HG-EOC case, we have generated PDX and a cell line. We will study in vivo and in vitro drug response to FGFR inhibition and other relevant therapeutics. Furthermore, we will conduct detailed molecular characterization of the baseline patient tumour, the PDX and the cell line to further understand drug response and resistance.