The out-of-field dose in radiation therapy induces delayed tumorigenesis by senescence evasion.
cancer biology
cell biology
dna double-strand breaks
dna repair
dna single-strand breaks
normal human dermal fibroblasts
parp
radiotherapy
sarcoma
second primary cancer
senescence
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
18 03 2022
18 03 2022
Historique:
received:
03
02
2021
accepted:
15
02
2022
entrez:
18
3
2022
pubmed:
19
3
2022
medline:
30
4
2022
Statut:
epublish
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.
Identifiants
pubmed: 35302491
doi: 10.7554/eLife.67190
pii: 67190
pmc: PMC8933005
doi:
pii:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2022, Goy et al.
Déclaration de conflit d'intérêts
EG, MT, CF, NM, EB, JB, Cd, JN, LS, CD, PB, AV, OM, LP, GG, OP, AP, FC, EL, NP, CA No competing interests declared
Références
EBioMedicine. 2017 Jul;21:21-28
pubmed: 28416161
Nature. 2011 Nov 02;479(7372):232-6
pubmed: 22048312
Radiother Oncol. 2009 Apr;91(1):4-15; discussion 1-3
pubmed: 19201045
Strahlenther Onkol. 2009 Oct;185(10):696-702
pubmed: 19806336
PLoS One. 2010 Sep 14;5(9):e12712
pubmed: 20856861
Int J Radiat Oncol Biol Phys. 2009 Jul 1;74(3):876-83
pubmed: 19386434
Int J Radiat Biol. 2000 Jan;76(1):67-75
pubmed: 10665959
J Natl Cancer Inst. 2010 Jul 21;102(14):1083-95
pubmed: 20634481
Eur J Cancer. 2014 Jul;50(10):1779-1788
pubmed: 24731859
J Natl Cancer Inst. 2009 Jun 3;101(11):806-13
pubmed: 19470947
Physiol Res. 2011;60(4):667-77
pubmed: 21574764
Int J Cancer. 2012 Apr 15;130(8):1715-25
pubmed: 22025288
Phys Med Biol. 2007 Jun 21;52(12):3563-78
pubmed: 17664560
Int J Radiat Oncol Biol Phys. 2013 Jun 1;86(2):224-33
pubmed: 23102695
J Vet Sci. 2012 Dec;13(4):331-8
pubmed: 23271173
Cell. 2017 Jun 1;169(6):1000-1011
pubmed: 28575665
Cell Mol Life Sci. 2017 Dec;74(24):4471-4509
pubmed: 28707011
Radiat Environ Biophys. 1994;33(1):45-61
pubmed: 8202592
Oncogene. 2003 Oct 13;22(45):6988-93
pubmed: 14557802
Cancer. 2019 Apr 15;125(8):1373-1383
pubmed: 30556153
Clin Cancer Res. 2007 May 1;13(9):2728-37
pubmed: 17473206
Cancer Lett. 2012 Dec 31;327(1-2):48-60
pubmed: 22182453
Am J Physiol Cell Physiol. 2015 Mar 15;308(6):C415-25
pubmed: 25540175
Curr Opin Chem Biol. 1999 Feb;3(1):77-83
pubmed: 10021401
Cell. 2005 Feb 25;120(4):513-22
pubmed: 15734683
Oncogene. 2004 Apr 12;23(16):2919-33
pubmed: 15077154
Am J Pathol. 2009 Feb;174(2):423-35
pubmed: 19147823
Cell Cycle. 2015;14(3):297-304
pubmed: 25564883
Nat Rev Genet. 2008 Aug;9(8):619-31
pubmed: 18626472
Annu Rev Pharmacol Toxicol. 2001;41:367-401
pubmed: 11264462
Clin Radiol. 2001 Jan;56(1):22-9
pubmed: 11162693
Adv Exp Med Biol. 1980;129:31-8
pubmed: 7395634
Trends Cell Biol. 2001 Nov;11(11):S27-31
pubmed: 11684439
Cancer Res. 2009 Oct 15;69(20):7917-25
pubmed: 19826058
Nat Rev Mol Cell Biol. 2007 Sep;8(9):729-40
pubmed: 17667954
Mol Cancer. 2014 Jun 14;13:151
pubmed: 24929818
FEBS J. 2020 Jun;287(12):2418-2427
pubmed: 32112672
Ann N Y Acad Sci. 2007 Nov;1119:51-63
pubmed: 18056954
Cancer Epidemiol Biomarkers Prev. 2006 Nov;15(11):2020-6
pubmed: 17057028
J Appl Clin Med Phys. 2016 Sep 08;17(5):124-132
pubmed: 27685104
Cancer. 2005 Aug 15;104(4):856-63
pubmed: 15981282
Z Med Phys. 2011 Sep;21(3):183-97
pubmed: 21530198
Int J Biochem Cell Biol. 2005 May;37(5):961-76
pubmed: 15743671
Nat Med. 2016 Jan;22(1):78-83
pubmed: 26657143
Exp Cell Res. 2014 Nov 15;329(1):2-8
pubmed: 25176342
Phys Med Biol. 2012 Mar 21;57(6):1733-43
pubmed: 22398213
Antioxid Redox Signal. 2014 Jul 10;21(2):260-92
pubmed: 24382094
Int J Radiat Oncol Biol Phys. 2017 Oct 1;99(2):353-361
pubmed: 28479002
Phys Med. 2017 Oct;42:221-227
pubmed: 29103987
Curr Opin Genet Dev. 2014 Jun;26:89-95
pubmed: 25104620
Int J Mol Sci. 2013 Jul 31;14(8):15931-58
pubmed: 23912235
Cell Rep. 2015 Sep 1;12(9):1483-96
pubmed: 26299965
Br J Surg. 2017 Feb;104(3):278-287
pubmed: 27802358
J Radiol Prot. 2002 Sep;22(3A):A117-21
pubmed: 12400959
Cancer Radiother. 2010 Jan;14(1):74-80
pubmed: 19963424
Cancer Radiother. 2010 Jul;14(4-5):255-62
pubmed: 20598615
PLoS One. 2013 May 10;8(5):e63607
pubmed: 23675494
Nat Commun. 2016 Jan 29;7:10399
pubmed: 26822533
Nature. 2003 Nov 13;426(6963):194-8
pubmed: 14608368
Med Phys. 2007 Sep;34(9):3489-99
pubmed: 17926952
Cancer. 1988 Feb 15;61(4):679-88
pubmed: 3338033