Rendering DNA Repair Defective by Targeting Wild-type BRCA1 Nuclear Shuttling in Sporadic Breast Cancer as a Therapeutic Agent

2009 ◽  
Author(s):  
Fen Xia
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Sporadic Breast Cancer ◽  
Therapeutic Agent ◽  
Wild Type ◽  
Nuclear Shuttling

DNA repair polymorphisms might contribute differentially on familial and sporadic breast cancer susceptibility: a study on a Portuguese population

2006 ◽  
Vol 103 (2) ◽  
pp. 209-217 ◽  
Author(s):  
Sandra Costa ◽  
Daniela Pinto ◽  
Deolinda Pereira ◽  
Helena Rodrigues ◽  
Jorge Cameselle-Teijeiro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Sporadic Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Portuguese Population

scholarly journals Association of Rad51 polymorphism with DNA repair in BRCA1 mutation carriers and sporadic breast cancer risk

BMC Cancer ◽  
2011 ◽  
Vol 11 (1) ◽  
Author(s):  
Luisel J Ricks-Santi ◽  
Lara E Sucheston ◽  
Yang Yang ◽  
Jo L Freudenheim ◽  
Claudine J Isaacs ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Sporadic Breast Cancer ◽  
Brca1 Mutation ◽  
Mutation Carriers

scholarly journals Efficacy and pharmacodynamics of niraparib in BRCA-mutant and wild-type intracranial triple-negative breast cancer murine models

2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Maria J Sambade ◽  
Amanda E D Van Swearingen ◽  
Marni B McClure ◽  
Allison M Deal ◽  
Charlene Santos ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Brain Metastases ◽  
Mouse Models ◽  
Cell Lines ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibition ◽  
Wild Type ◽  
Tnbc Cell

Abstract Background Despite the poor prognosis of triple-negative breast cancer (TNBC) brain metastases, there are no approved systemic therapies. We explored the DNA-damaging poly(ADP-ribose) polymerase inhibitor (PARPi) niraparib in intracranial mouse models of breast cancer susceptibility protein (BRCA)-mutant TNBC. Methods Mice bearing intracranial human-derived TNBC cell lines (SUM149, MDA-MB-231Br, or MDA-MB-436) were treated with niraparib and monitored for survival; intracranial tissues were analyzed for PAR levels and niraparib concentration by mass spectrometry. RNASeq data of primary breast cancers using The Cancer Genome Atlas were analyzed for DNA damage signatures. Combined RAD51 and PARP inhibition in TNBC cell lines was assessed in vitro by colony-forming assays. Results Daily niraparib increased median survival and decreased tumor burden in the BRCA-mutant MDA-MB-436 model, but not in the BRCA-mutant SUM149 or BRCA-wild-type MDA-MB-231Br models despite high concentrations in intracranial tumors. RAD51 inhibitor B02 was shown to sensitize all cell lines to PARP inhibition (PARPi). In the analysis of BRCA-mutant primary human TNBCs, gene expression predictors of PARPi sensitivity and DNA repair signatures demonstrate widespread heterogeneity, which may explain the differential response to PARPi. Interestingly, these signatures are significantly correlated to RAD51 expression including PARPi sensitivity (R2 = 0.602, R2= 0.758). Conclusions Niraparib penetrates intracranial tumor tissues in mouse models of TNBC with impressive single-agent efficacy in BRCA-mutant MDA-MB-436. Clinical evaluation of niraparib to treat TNBC brain metastases, an unmet clinical need desperate for improved therapies, is warranted. Further compromising DNA repair through RAD51 inhibition may further augment TNBC’s response to PARPi.

scholarly journals Personalised pathway analysis reveals association between DNA repair pathway dysregulation and chromosomal instability in sporadic breast cancer

2015 ◽  
Vol 10 (1) ◽  
pp. 179-193 ◽  
Author(s):  
Chao Liu ◽  
Sriganesh Srihari ◽  
Samir Lal ◽  
Benoît Gautier ◽  
Peter T. Simpson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Pathway Analysis ◽  
Chromosomal Instability ◽  
Sporadic Breast Cancer ◽  
Repair Pathway ◽  
Pathway Dysregulation

scholarly journals DNA repair gene XRCC3 241Met variant and breast cancer susceptibility of Azeri population in Iranian

Genetika ◽  
2015 ◽  
Vol 47 (2) ◽  
pp. 733-739 ◽  
Author(s):  
Sahar Gohari-Lasaki ◽  
Jalal Gharesouran ◽  
Morteza Ghojazadeh ◽  
Vahid Montazeri ◽  
Hakimeh Saadatian ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Sporadic Breast Cancer ◽  
Cancer Susceptibility ◽  
Breast Cancer Susceptibility ◽  
Breast Cancer Patients ◽  
Repair Gene ◽  
Allele Distribution ◽  
Dna Repair Gene ◽  
Xrcc3 Thr241met

DNA-repair systems are essential for repairing damage that occurs when there is recombination between homologous chromosomes. The gene XRCC3 (X-ray cross complementing group 3) encodes a member of the RecA/Rad51-related protein family that participates in homologous recombination to maintain chromosome stability and repair DNA damage. The Thr241Met XRCC3-18067C>T, rs861539) substitution, a C to T transition at codon 241 in exon7, thus plays critical roles in cancer development. The aim of this study was association between XRCC3 Thr241Met polymorphism and risk of sporadic breast cancer in Azari population. We analysed DNA samples from 100 sporadic breast cancer patients and 100 healthy women, for XRCC3 Thr241Met polymorphism using PCR-RFLP. Genotype specific risks were tested using chi-test with 95% confident intervals. Frequency of Thr/Thr at codon 241was 69% in controls and 70% in patients, Thr/Met frequency was 22% in controls and 13 % in patients, the Met/Met genotype was 9% incontrols and 17% in patients. No correlation between the genotype and allele distribution and increased susceptibility for breast Cancer. Our results suggested that in pre-menopausal women, breast cancer riskis not significantly associated with rs861539 in Azari population.

DNA Repair Genes XRCC1 and ERCC1 Polymorphisms and the Risk of Sporadic Breast Cancer in Han Women in the Gansu Province of China

2015 ◽  
Vol 19 (7) ◽  
pp. 387-393 ◽  
Author(s):  
Gongjian Zhu ◽  
Lan Wang ◽  
Hongyun Guo ◽  
Lingeng Lu ◽  
Suisheng Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Sporadic Breast Cancer ◽  
Gansu Province ◽  
Dna Repair Genes ◽  
Repair Genes

Truncating variants in DNA-repair genes and their effect on AAO of hereditary breast cancer

2018 ◽  
Author(s):  
I Sepahi ◽  
U Faust ◽  
M Sturm ◽  
K Bosse ◽  
M Kehrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Repair ◽  
Hereditary Breast Cancer ◽  
Dna Repair Genes ◽  
Repair Genes
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