Tumorgrafts as In Vivo Surrogates for Women with Ovarian Cancer

SJ Weroha, MA Becker, S Enderica-Gonzalez… - Clinical Cancer …, 2014 - AACR
SJ Weroha, MA Becker, S Enderica-Gonzalez, SC Harrington, AL Oberg, MJ Maurer
Clinical Cancer Research, 2014AACR
Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved
outcomes includes a lack of accurate models for preclinical testing of novel therapeutics.
Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated
from sequential patients and the first 168 engrafted models are described. Fresh ovarian,
primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking
surgery and injected intraperitoneally into severe combined immunodeficient mice. Results …
Abstract
Purpose: Ovarian cancer has a high recurrence and mortality rate. A barrier to improved outcomes includes a lack of accurate models for preclinical testing of novel therapeutics.
Experimental Design: Clinically relevant, patient-derived tumorgraft models were generated from sequential patients and the first 168 engrafted models are described. Fresh ovarian, primary peritoneal, and fallopian tube carcinomas were collected at the time of debulking surgery and injected intraperitoneally into severe combined immunodeficient mice.
Results: Tumorgrafts demonstrated a 74% engraftment rate with microscopic fidelity of primary tumor characteristics. Low-passage tumorgrafts also showed comparable genomic aberrations with the corresponding primary tumor and exhibit gene set enrichment of multiple ovarian cancer molecular subtypes, similar to patient tumors. Importantly, each of these tumorgraft models is annotated with clinical data and for those that have been tested, response to platinum chemotherapy correlates with the source patient.
Conclusions: Presented herein is the largest known living tumor bank of patient-derived, ovarian tumorgraft models that can be applied to the development of personalized cancer treatment. Clin Cancer Res; 20(5); 1288–97. ©2014 AACR.
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