Radiosensitivity Is an Acquired Vulnerability of PARPi-Resistant BRCA1-Deficient Tumors.
Animals
BRCA1 Protein
Cell Cycle Proteins
/ genetics
DNA Repair
/ drug effects
DNA-Binding Proteins
/ genetics
Disease Models, Animal
Drug Resistance, Neoplasm
/ genetics
Gene Expression Regulation, Neoplastic
/ drug effects
Homologous Recombination
/ genetics
Humans
Mad2 Proteins
/ genetics
Mice
Neoplasms
/ drug therapy
Poly(ADP-ribose) Polymerase Inhibitors
/ pharmacology
Poly(ADP-ribose) Polymerases
/ genetics
Radiation Tolerance
/ genetics
Telomere-Binding Proteins
/ genetics
Tumor Suppressor Proteins
/ genetics
Tumor Suppressor p53-Binding Protein 1
/ genetics
Journal
Cancer research
ISSN: 1538-7445
Titre abrégé: Cancer Res
Pays: United States
ID NLM: 2984705R
Informations de publication
Date de publication:
01 02 2019
01 02 2019
Historique:
received:
12
07
2018
revised:
05
10
2018
accepted:
03
12
2018
pubmed:
12
12
2018
medline:
9
11
2019
entrez:
12
12
2018
Statut:
ppublish
Résumé
The defect in homologous recombination (HR) found in BRCA1-associated cancers can be therapeutically exploited by treatment with DNA-damaging agents and PARP inhibitors. We and others previously reported that BRCA1-deficient tumors are initially hypersensitive to the inhibition of topoisomerase I/II and PARP, but acquire drug resistance through restoration of HR activity by the loss of end-resection antagonists of the 53BP1/RIF1/REV7/Shieldin/CST pathway. Here, we identify radiotherapy as an acquired vulnerability of 53BP1;BRCA1-deficient cells
Identifiants
pubmed: 30530501
pii: 0008-5472.CAN-18-2077
doi: 10.1158/0008-5472.CAN-18-2077
pmc: PMC6366562
mid: EMS80840
doi:
Substances chimiques
BRCA1 Protein
0
Brca1 protein, mouse
0
Cell Cycle Proteins
0
DNA-Binding Proteins
0
Mad2 Proteins
0
Mad2l2 protein, mouse
0
Poly(ADP-ribose) Polymerase Inhibitors
0
Rif1 protein, mouse
0
SHLD1 protein, human
0
Telomere-Binding Proteins
0
Trp53bp1 protein, mouse
0
Tumor Suppressor Proteins
0
Tumor Suppressor p53-Binding Protein 1
0
Poly(ADP-ribose) Polymerases
EC 2.4.2.30
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
452-460Informations de copyright
©2018 American Association for Cancer Research.
Références
Genes Dev. 1999 Apr 15;13(8):916-34
pubmed: 10215620
Nat Methods. 2018 Feb;15(2):134-140
pubmed: 29256493
Cell. 2018 May 3;173(4):972-988.e23
pubmed: 29656893
Mol Cell. 1998 Sep;2(3):317-28
pubmed: 9774970
Adv Cancer Res. 1963;7:235-50
pubmed: 14153767
Nat Rev Cancer. 2005 Sep;5(9):689-98
pubmed: 16110319
Cell Rep. 2015 Sep 29;12(12):1978-85
pubmed: 26365186
Science. 2013 Feb 15;339(6121):819-23
pubmed: 23287718
Cell. 2010 Apr 16;141(2):243-54
pubmed: 20362325
Cancer Res. 2010 Feb 15;70(4):1700-10
pubmed: 20145144
Nature. 2015 May 28;521(7553):541-544
pubmed: 25799992
Nucleic Acids Res. 2018 Apr 6;46(6):2945-2955
pubmed: 29447381
Med Phys. 2011 Feb;38(2):845-56
pubmed: 21452722
Nucleic Acids Res. 2014 Dec 16;42(22):e168
pubmed: 25300484
Science. 2017 Mar 17;355(6330):1152-1158
pubmed: 28302823
Cell. 2016 Sep 22;167(1):260-274.e22
pubmed: 27641504
Cell. 2008 Feb 8;132(3):487-98
pubmed: 18267078
DNA Repair (Amst). 2006 Jun 10;5(6):741-9
pubmed: 16644291
Cancer Discov. 2013 Jan;3(1):68-81
pubmed: 23103855
Proc Natl Acad Sci U S A. 2007 Jul 17;104(29):12111-6
pubmed: 17626182
Cell Rep. 2018 Apr 03;23(1):239-254.e6
pubmed: 29617664
Cell Rep. 2018 May 15;23(7):2107-2118
pubmed: 29768208
Nat Genet. 2000 Jun;25(2):217-22
pubmed: 10835641
Proc Natl Acad Sci U S A. 2008 Nov 4;105(44):17079-84
pubmed: 18971340
Mol Cell. 2013 Mar 7;49(5):858-71
pubmed: 23333305