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Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients

The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generate...

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Autores principales: Di Franco, Gregorio, Usai, Alice, Piccardi, Margherita, Cateni, Perla, Palmeri, Matteo, Pollina, Luca Emanuele, Gaeta, Raffaele, Marmorino, Federica, Cremolini, Chiara, Dente, Luciana, Massolo, Alessandro, Raffa, Vittoria, Morelli, Luca
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313122/
https://www.ncbi.nlm.nih.gov/pubmed/35884780
http://dx.doi.org/10.3390/biomedicines10071474
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author Di Franco, Gregorio
Usai, Alice
Piccardi, Margherita
Cateni, Perla
Palmeri, Matteo
Pollina, Luca Emanuele
Gaeta, Raffaele
Marmorino, Federica
Cremolini, Chiara
Dente, Luciana
Massolo, Alessandro
Raffa, Vittoria
Morelli, Luca
author_facet Di Franco, Gregorio
Usai, Alice
Piccardi, Margherita
Cateni, Perla
Palmeri, Matteo
Pollina, Luca Emanuele
Gaeta, Raffaele
Marmorino, Federica
Cremolini, Chiara
Dente, Luciana
Massolo, Alessandro
Raffa, Vittoria
Morelli, Luca
author_sort Di Franco, Gregorio
collection PubMed
description The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine.
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spelling pubmed-93131222022-07-26 Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients Di Franco, Gregorio Usai, Alice Piccardi, Margherita Cateni, Perla Palmeri, Matteo Pollina, Luca Emanuele Gaeta, Raffaele Marmorino, Federica Cremolini, Chiara Dente, Luciana Massolo, Alessandro Raffa, Vittoria Morelli, Luca Biomedicines Article The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine. MDPI 2022-06-22 /pmc/articles/PMC9313122/ /pubmed/35884780 http://dx.doi.org/10.3390/biomedicines10071474 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Di Franco, Gregorio
Usai, Alice
Piccardi, Margherita
Cateni, Perla
Palmeri, Matteo
Pollina, Luca Emanuele
Gaeta, Raffaele
Marmorino, Federica
Cremolini, Chiara
Dente, Luciana
Massolo, Alessandro
Raffa, Vittoria
Morelli, Luca
Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title_full Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title_fullStr Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title_full_unstemmed Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title_short Zebrafish Patient-Derived Xenograft Model to Predict Treatment Outcomes of Colorectal Cancer Patients
title_sort zebrafish patient-derived xenograft model to predict treatment outcomes of colorectal cancer patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9313122/
https://www.ncbi.nlm.nih.gov/pubmed/35884780
http://dx.doi.org/10.3390/biomedicines10071474
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