journal contribution
posted on 2023-03-31, 20:07 authored by Joyce F. Liu, Sangeetha Palakurthi, Qing Zeng, Shan Zhou, Elena Ivanova, Wei Huang, Ioannis K. Zervantonakis, Laura M. Selfors, Yiping Shen, Colin C. Pritchard, Mei Zheng, Vilmos Adleff, Eniko Papp, Huiying Piao, Marian Novak, Susan Fotheringham, Gerburg M. Wulf, Jessie English, Paul T. Kirschmeier, Victor E. Velculescu, Cloud Paweletz, Gordon B. Mills, David M. Livingston, Joan S. Brugge, Ursula A. Matulonis, Ronny Drapkin Table S1: Optimal conditions for PDX luciferization; Table S3: BROCA characterization; Table S6: PIK3CA FISH. Figure S1: Schema for PDX generation; Figures S2: IHC of DF68; Figure S3: Array CGH of DF86; Figure S4: PI3K pathway analysis from RPPA; Figure S5: Correlation between BLI and plasma CA125
Funding
Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
NIH
Honorable Tina Brozman Foundation
History
ARTICLE ABSTRACT
Purpose: Ovarian cancer is the leading cause of death from gynecologic malignancy in the United States, with high rates of recurrence and eventual resistance to cytotoxic chemotherapy. Model systems that allow for accurate and reproducible target discovery and validation are needed to support further drug development in this disease.Experimental Design: Clinically annotated patient-derived xenograft (PDX) models were generated from tumor cells isolated from the ascites or pleural fluid of patients undergoing clinical procedures. Models were characterized by IHC and by molecular analyses. Each PDX was luciferized to allow for reproducible in vivo assessment of intraperitoneal tumor burden by bioluminescence imaging (BLI). Plasma assays for CA125 and human LINE-1 were developed as secondary tests of in vivo disease burden.Results: Fourteen clinically annotated and molecularly characterized luciferized ovarian PDX models were generated. Luciferized PDX models retain fidelity to both the nonluciferized PDX and the original patient tumor, as demonstrated by IHC, array CGH, and targeted and whole-exome sequencing analyses. Models demonstrated diversity in specific genetic alterations and activation of PI3K signaling pathway members. Response of luciferized PDX models to standard-of-care therapy could be reproducibly monitored by BLI or plasma markers.Conclusions: We describe the establishment of a collection of 14 clinically annotated and molecularly characterized luciferized ovarian PDX models in which orthotopic tumor burden in the intraperitoneal space can be followed by standard and reproducible methods. This collection is well suited as a platform for proof-of-concept efficacy and biomarker studies and for validation of novel therapeutic strategies in ovarian cancer. Clin Cancer Res; 23(5); 1263–73. ©2016 AACR.
