Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine
Background: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living c...
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doaj-8aae517129504fe0989349fa9e6264ff2020-11-25T01:01:09ZengElsevierEBioMedicine2352-39642020-01-0151Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicineBruna Costa0Susana Ferreira1Vanda Póvoa2Maria João Cardoso3Sandra Vieira4Joep Stroom5Paulo Fidalgo6Ricardo Rio-Tinto7Nuno Figueiredo8Oriol Parés9Carlo Greco10Miguel Godinho Ferreira11Rita Fior12Champalimaud Centre for the Unknown, Champalimaud Foundation, Av Brasilia, 1400-038 Lisbon, PortugalChampalimaud Centre for the Unknown, Champalimaud Foundation, Av Brasilia, 1400-038 Lisbon, PortugalChampalimaud Centre for the Unknown, Champalimaud Foundation, Av Brasilia, 1400-038 Lisbon, PortugalRadiation Oncology Department, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalRadiation Oncology Department, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalRadiation Oncology Department, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalDigestive Unit, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalDigestive Unit, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalDigestive Unit, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalRadiation Oncology Department, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalRadiation Oncology Department, Champalimaud Clinical Centre, Champalimaud Foundation, 1400-038 Lisbon, PortugalChampalimaud Centre for the Unknown, Champalimaud Foundation, Av Brasilia, 1400-038 Lisbon, Portugal; Université Côte d'Azur, Institute for Research on Cancer and Aging of Nice (IRCAN), CNRS UMR7284 INSERM U1081, 06107 Nice, France; Corresponding authors.Champalimaud Centre for the Unknown, Champalimaud Foundation, Av Brasilia, 1400-038 Lisbon, Portugal; Corresponding authors.Background: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. Methods: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. Findings: By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. Interpretation: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity. Keywords: Chemoradiotherapy, Colorectal cancer, Zebrafish avatars, Personalized medicine, Radiotherapyhttp://www.sciencedirect.com/science/article/pii/S2352396419307881 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Bruna Costa Susana Ferreira Vanda Póvoa Maria João Cardoso Sandra Vieira Joep Stroom Paulo Fidalgo Ricardo Rio-Tinto Nuno Figueiredo Oriol Parés Carlo Greco Miguel Godinho Ferreira Rita Fior |
spellingShingle |
Bruna Costa Susana Ferreira Vanda Póvoa Maria João Cardoso Sandra Vieira Joep Stroom Paulo Fidalgo Ricardo Rio-Tinto Nuno Figueiredo Oriol Parés Carlo Greco Miguel Godinho Ferreira Rita Fior Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine EBioMedicine |
author_facet |
Bruna Costa Susana Ferreira Vanda Póvoa Maria João Cardoso Sandra Vieira Joep Stroom Paulo Fidalgo Ricardo Rio-Tinto Nuno Figueiredo Oriol Parés Carlo Greco Miguel Godinho Ferreira Rita Fior |
author_sort |
Bruna Costa |
title |
Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
title_short |
Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
title_full |
Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
title_fullStr |
Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
title_full_unstemmed |
Developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
title_sort |
developments in zebrafish avatars as radiotherapy sensitivity reporters — towards personalized medicine |
publisher |
Elsevier |
series |
EBioMedicine |
issn |
2352-3964 |
publishDate |
2020-01-01 |
description |
Background: Whereas the role of neoadjuvant radiotherapy in rectal cancer is well-established, the ability to discriminate between radioresistant and radiosensitive tumors before starting treatment is still a crucial unmet need. Here we aimed to develop an in vivo test to directly challenge living cancer cells to radiotherapy, using zebrafish xenografts. Methods: We generated zebrafish xenografts using colorectal cancer cell lines and patient biopsies without in vitro passaging, and developed a fast radiotherapy protocol consisting of a single dose of 25 Gy. As readouts of the impact of radiotherapy we analyzed proliferation, apoptosis, tumor size and DNA damage. Findings: By directly comparing isogenic cells that only differ in the KRASG13D allele, we show that it is possible to distinguish radiosensitive from radioresistant tumors in zebrafish xenografts, even in polyclonal tumors, in just 4 days. Most importantly, we performed proof-of-concept experiments using primary rectum biopsies, where clinical response to neoadjuvant chemoradiotherapy correlates with induction of apoptosis in their matching zebrafish Patient-Derived Xenografts-Avatars. Interpretation: Our work opens the possibility to predict tumor responses to radiotherapy using the zebrafish Avatar model, sparing valuable therapeutic time and unnecessary toxicity. Keywords: Chemoradiotherapy, Colorectal cancer, Zebrafish avatars, Personalized medicine, Radiotherapy |
url |
http://www.sciencedirect.com/science/article/pii/S2352396419307881 |
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