TY - JOUR
T1 - Zebrafish Avatars of rectal cancer patients validate the radiosensitive effect of metformin
AU - Costa, Bruna
AU - Fernandez, Laura M.
AU - Parés, Oriol
AU - Rio-Tinto, Ricardo
AU - Santiago, Inês
AU - Castillo-Martin, Mireia
AU - Parvaiz, Amjad
AU - Fior, Rita
N1 - Publisher Copyright:
Copyright © 2022 Costa, Fernandez, Parés, Rio-Tinto, Santiago, Castillo-Martin, Parvaiz and Fior.
PY - 2022/9/28
Y1 - 2022/9/28
N2 - 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.
AB - 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.
KW - metformin
KW - neoadjuvant chemoradiation
KW - radiotherapy
KW - rectal cancer
KW - zebrafish Avatars
UR - http://www.scopus.com/inward/record.url?scp=85139755774&partnerID=8YFLogxK
U2 - 10.3389/fonc.2022.862889
DO - 10.3389/fonc.2022.862889
M3 - Article
AN - SCOPUS:85139755774
SN - 2234-943X
VL - 12
JO - Frontiers in Oncology
JF - Frontiers in Oncology
M1 - 862889
ER -