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The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion

A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1–40 years. We show here that normal human...

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Autores principales: Goy, Erwan, Tomezak, Maxime, Facchin, Caterina, Martin, Nathalie, Bouchaert, Emmanuel, Benoit, Jerome, de Schutter, Clementine, Nassour, Joe, Saas, Laure, Drullion, Claire, Brodin, Priscille M, Vandeputte, Alexandre, Molendi-Coste, Olivier, Pineau, Laurent, Goormachtigh, Gautier, Pluquet, Olivier, Pourtier, Albin, Cleri, Fabrizio, Lartigau, Eric, Penel, Nicolas, Abbadie, Corinne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933005/
https://www.ncbi.nlm.nih.gov/pubmed/35302491
http://dx.doi.org/10.7554/eLife.67190
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author Goy, Erwan
Tomezak, Maxime
Facchin, Caterina
Martin, Nathalie
Bouchaert, Emmanuel
Benoit, Jerome
de Schutter, Clementine
Nassour, Joe
Saas, Laure
Drullion, Claire
Brodin, Priscille M
Vandeputte, Alexandre
Molendi-Coste, Olivier
Pineau, Laurent
Goormachtigh, Gautier
Pluquet, Olivier
Pourtier, Albin
Cleri, Fabrizio
Lartigau, Eric
Penel, Nicolas
Abbadie, Corinne
author_facet Goy, Erwan
Tomezak, Maxime
Facchin, Caterina
Martin, Nathalie
Bouchaert, Emmanuel
Benoit, Jerome
de Schutter, Clementine
Nassour, Joe
Saas, Laure
Drullion, Claire
Brodin, Priscille M
Vandeputte, Alexandre
Molendi-Coste, Olivier
Pineau, Laurent
Goormachtigh, Gautier
Pluquet, Olivier
Pourtier, Albin
Cleri, Fabrizio
Lartigau, Eric
Penel, Nicolas
Abbadie, Corinne
author_sort Goy, Erwan
collection PubMed
description A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1–40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient’s treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention.
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spelling pubmed-89330052022-03-19 The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion Goy, Erwan Tomezak, Maxime Facchin, Caterina Martin, Nathalie Bouchaert, Emmanuel Benoit, Jerome de Schutter, Clementine Nassour, Joe Saas, Laure Drullion, Claire Brodin, Priscille M Vandeputte, Alexandre Molendi-Coste, Olivier Pineau, Laurent Goormachtigh, Gautier Pluquet, Olivier Pourtier, Albin Cleri, Fabrizio Lartigau, Eric Penel, Nicolas Abbadie, Corinne eLife Cancer Biology A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1–40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient’s treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention. eLife Sciences Publications, Ltd 2022-03-18 /pmc/articles/PMC8933005/ /pubmed/35302491 http://dx.doi.org/10.7554/eLife.67190 Text en © 2022, Goy et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cancer Biology
Goy, Erwan
Tomezak, Maxime
Facchin, Caterina
Martin, Nathalie
Bouchaert, Emmanuel
Benoit, Jerome
de Schutter, Clementine
Nassour, Joe
Saas, Laure
Drullion, Claire
Brodin, Priscille M
Vandeputte, Alexandre
Molendi-Coste, Olivier
Pineau, Laurent
Goormachtigh, Gautier
Pluquet, Olivier
Pourtier, Albin
Cleri, Fabrizio
Lartigau, Eric
Penel, Nicolas
Abbadie, Corinne
The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title_full The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title_fullStr The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title_full_unstemmed The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title_short The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
title_sort out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion
topic Cancer Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8933005/
https://www.ncbi.nlm.nih.gov/pubmed/35302491
http://dx.doi.org/10.7554/eLife.67190
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