In:
Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 26, No. 11_Supplement ( 2020-06-01), p. B25-B25
Abstract:
Ovarian cancer is characterized by poor prognosis and high relapse rate, unfortunately accompanied with resistance to previously used therapy. Currently, resistance is defined by the time between treatment and progression of the disease. A better model to test resistance is to make patient-derived xenografts (PDX). We propose here the development of a PDX platform in zebrafish. This model allows testing of both previously used treatment and possible other treatment strategies. The fast readout of less than 15 days and the limited amount of material required (few 100s of cells) allow implementation in clinical practice. In a first phase, a correlation study will be performed to establish that zebrafish PDX models mimic the response of the patient to adjuvant chemotherapy by using primary tumor tissue. In the second phase of this project, circulating tumor cells will be isolated at different time points during treatment and follow-up. The objective of this part of the study is to isolate and cultivate CTCs for engraftment. For this we will apply a recently introduced size-based separation method (MetaCell®). The viable cells will undergo a short in vitro culture to expand and to get rid of remaining lymphocytes. Possible changes in mesenchymal-to-epithelial transition are picked up by single-cell sequencing (10xGenomics®) of the cells prior and post culturing. After culturing the CTCs are fluorescently labeled and engrafted into two-day-old zebrafish embryos. Tumors are formed the following day and treated with different treatment options for three executive days. Tumor proliferation and growth is observed in vivo through fluorescence microscopy. Post-mortem readouts are based on immunohistochemistry profiles. Resistance is defined by high proliferation rate (Ki-67) and mitotic index and low apoptosis rate (Caspase-3). Comparative morphology with primary tissue and CTC-PDX is evaluated by hematoxylin and eosin staining on FFPE-slices. This methodology may provide an opportunity for more personalized medicine in which treatment for OC may be guided by information from an individual’s zebrafish PDX response to therapy. Citation Format: Charlotte Fieuws, Jeroen Vierstraete, Koen Van De Vijver, Hannelore Denys, Kathleen BM Claes. Isolation and engraftment of circulating tumor cells into zebrafish embryos to predict tumor response of ovarian cancer patients [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr B25.
Type of Medium:
Online Resource
ISSN:
1078-0432
,
1557-3265
DOI:
10.1158/1557-3265.LiqBiop20-B25
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2020
detail.hit.zdb_id:
1225457-5
detail.hit.zdb_id:
2036787-9
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