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Data from Establishment of Patient-Derived Tumor Xenograft Models of Epithelial Ovarian Cancer for Preclinical Evaluation of Novel Therapeutics

Authors :
Ronny Drapkin
Ursula A. Matulonis
Joan S. Brugge
David M. Livingston
Gordon B. Mills
Cloud Paweletz
Victor E. Velculescu
Paul T. Kirschmeier
Jessie English
Gerburg M. Wulf
Susan Fotheringham
Marian Novak
Huiying Piao
Eniko Papp
Vilmos Adleff
Mei Zheng
Colin C. Pritchard
Yiping Shen
Laura M. Selfors
Ioannis K. Zervantonakis
Wei Huang
Elena Ivanova
Shan Zhou
Qing Zeng
Sangeetha Palakurthi
Joyce F. Liu
Publication Year :
2023
Publisher :
American Association for Cancer Research (AACR), 2023.

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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi.dedup.....5b2a05453f520d38aebed6500d1591f4
Full Text :
https://doi.org/10.1158/1078-0432.c.6526395