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Article Dans Une Revue eLife Année : 2022

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

Résumé

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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hal-03613878 , version 1 (19-05-2022)

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Erwan Goy, Maxime Tomezak, Caterina Facchin, Nathalie Martin, Emmanuel Bouchaert, et al.. The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion. eLife, 2022, 11 (e67190), ⟨10.7554/eLife.67190⟩. ⟨hal-03613878⟩
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