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Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin

Neoadjuvant chemoradiation (nCRT) followed by surgery represents the standard of care in patients with locally advanced rectal cancer. Increasing radiotherapy (RT) doses and chemotherapy cycles with 5FU have been associated with increased rates of complete response, however these strategies imply si...

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Autores principales: Costa, Bruna, Fernandez, Laura M., Parés, Oriol, Rio-Tinto, Ricardo, Santiago, Inês, Castillo-Martin, Mireia, Parvaiz, Amjad, Fior, Rita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554544/
https://www.ncbi.nlm.nih.gov/pubmed/36249066
http://dx.doi.org/10.3389/fonc.2022.862889
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author Costa, Bruna
Fernandez, Laura M.
Parés, Oriol
Rio-Tinto, Ricardo
Santiago, Inês
Castillo-Martin, Mireia
Parvaiz, Amjad
Fior, Rita
author_facet Costa, Bruna
Fernandez, Laura M.
Parés, Oriol
Rio-Tinto, Ricardo
Santiago, Inês
Castillo-Martin, Mireia
Parvaiz, Amjad
Fior, Rita
author_sort Costa, Bruna
collection PubMed
description Neoadjuvant chemoradiation (nCRT) followed by surgery represents the standard of care in patients with locally advanced rectal cancer. Increasing radiotherapy (RT) doses and chemotherapy cycles with 5FU have been associated with increased rates of complete response, however these strategies imply significant toxicity. In the last years, epidemiologic findings have demonstrated that metformin is associated with significantly higher rates of pathological complete response to nCRT. Also, pre-clinical studies using cell lines provide evidence for the radiosensitive effect of metformin. However, no studies have been performed using rectal cancer patient samples to test this radiosensitive effect of metformin and compared it to the standard 5FU. Here, we designed an experimental study to compare both radiosensitizers in the zebrafish xenograft model (zAvatar), using rectal cancer surgical specimens and diagnostic biopsies. Patient zAvatars confirmed that metformin has indeed a powerful in vivo radiosensitizer effect, similar to 5FU. Our work confirms that metformin constitutes a promising less toxic alternative to the standard 5FU, which could be game changing in elderly/frail patients to optimize tumor regression.
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spelling pubmed-95545442022-10-13 Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin Costa, Bruna Fernandez, Laura M. Parés, Oriol Rio-Tinto, Ricardo Santiago, Inês Castillo-Martin, Mireia Parvaiz, Amjad Fior, Rita Front Oncol Oncology Neoadjuvant chemoradiation (nCRT) followed by surgery represents the standard of care in patients with locally advanced rectal cancer. Increasing radiotherapy (RT) doses and chemotherapy cycles with 5FU have been associated with increased rates of complete response, however these strategies imply significant toxicity. In the last years, epidemiologic findings have demonstrated that metformin is associated with significantly higher rates of pathological complete response to nCRT. Also, pre-clinical studies using cell lines provide evidence for the radiosensitive effect of metformin. However, no studies have been performed using rectal cancer patient samples to test this radiosensitive effect of metformin and compared it to the standard 5FU. Here, we designed an experimental study to compare both radiosensitizers in the zebrafish xenograft model (zAvatar), using rectal cancer surgical specimens and diagnostic biopsies. Patient zAvatars confirmed that metformin has indeed a powerful in vivo radiosensitizer effect, similar to 5FU. Our work confirms that metformin constitutes a promising less toxic alternative to the standard 5FU, which could be game changing in elderly/frail patients to optimize tumor regression. Frontiers Media S.A. 2022-09-28 /pmc/articles/PMC9554544/ /pubmed/36249066 http://dx.doi.org/10.3389/fonc.2022.862889 Text en Copyright © 2022 Costa, Fernandez, Parés, Rio-Tinto, Santiago, Castillo-Martin, Parvaiz and Fior https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Costa, Bruna
Fernandez, Laura M.
Parés, Oriol
Rio-Tinto, Ricardo
Santiago, Inês
Castillo-Martin, Mireia
Parvaiz, Amjad
Fior, Rita
Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title_full Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title_fullStr Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title_full_unstemmed Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title_short Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
title_sort zebrafish avatars of rectal cancer patients validate the radiosensitive effect of metformin
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9554544/
https://www.ncbi.nlm.nih.gov/pubmed/36249066
http://dx.doi.org/10.3389/fonc.2022.862889
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