The use of patient-derived xenograft models for prioritizing therapeutic targets.

5579 Background: Treatment options for women with high-grade serous ovarian cancer (HGSC) remain limited. Defective DNA repair capability may underlie response to standard chemotherapy and to PARP inhibitor therapy1,2. Thus, molecular characterization of HGSC may indicate likely sensitivity or resistance to therapeutics. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Pre-clinical HGSC cell lines have been shown to poorly reflect human disease3 and rarely contain DNA repair gene mutations4. In contrast, patient-derived xenograft (PDX) models provide relevant, accurate and tractable models for pre-clinical testing, representative of patient outcome5,6. Methods: A patient derived xenograft (PDX) cohort was generated from consecutive, treatment-naive human HGSC and stratified according to DNA repair capability including BROCA sequencing7 and next generation sequencing by Foundation Medicine. In vivo response to standard chemothera...