Cargando…
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...
Autores principales: | , , , , , , , |
---|---|
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 |
_version_ | 1784806722079031296 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9554544 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT costabruna zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT fernandezlauram zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT paresoriol zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT riotintoricardo zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT santiagoines zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT castillomartinmireia zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT parvaizamjad zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin AT fiorrita zebrafishavatarsofrectalcancerpatientsvalidatetheradiosensitiveeffectofmetformin |