RT Journal Article SR Electronic T1 Biomarker-guided treatment strategies for ovarian cancer identified from a heterogeneous panel of patient-derived tumor xenografts JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.01.08.898734 DO 10.1101/2020.01.08.898734 A1 Adam C. Palmer A1 Deborah Plana A1 Hui Gao A1 Joshua M Korn A1 Guizhi Yang A1 John Green A1 Xiamei Zhang A1 Roberto Velazquez A1 Margaret E McLaughlin A1 David A Ruddy A1 Colleen Kowal A1 Julie Goldovitz A1 Caroline Bullock A1 Stacy Rivera A1 Daniel Rakiec A1 GiNell Elliott A1 Paul Fordjour A1 Ronald Meyer A1 Alice Loo A1 Esther Kurth A1 Jeffrey A Engelman A1 Hans Bitter A1 William R Sellers A1 Peter K Sorger A1 Juliet A Williams YR 2020 UL http://biorxiv.org/content/early/2020/01/13/2020.01.08.898734.abstract AB Advanced ovarian cancers are a leading cause of cancer-related death in women. Such cancers are currently treated with surgery and chemotherapy which is often temporarily successful but exhibits a high rate of relapse after which treatment options are few. Here we assess the responses of a panel of patient-derived ovarian cancer xenografts (PDXs) to 19 mono and combination therapies, including small molecules and antibody-drug conjugates. The PDX panel aimed to mimic the heterogeneity of disease observed in patients, and exhibited a distribution of responsiveness to standard of care chemotherapy similar to human clinical data. Three monotherapies and one drug combination were found to be active in different subsets of PDXs. By analyzing gene expression data we identified gene expression biomarkers predictive of responsiveness to each of three novel targeted therapy regimens. While no single treatment had as high a response rate as chemotherapy, nearly 90% of PDXs were eligible for and responded to at least one biomarker-guided treatment, including tumors resistant to standard chemotherapy. Biomarker frequency was similar in human patients, suggesting the possibility of a new therapeutic approach to ovarian cancer and demonstrating the potential power of PDX-based trials in broadening the reach of precision cancer medicine.