Resistance to therapy caused by intragenic deletion in BRCA2

By S. Edwards, R. Brough, C. Lord, R. Natrajan, R. Vatcheva, D. Levine, J. Boyd, J. Reis-Filho, Alan Ashworth. Nature, 2008

1,036 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/ccf6cffaa631fb2518b32ee5ab4ae97e831752fa

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Citations in the corpus

Molecular mechanisms of cisplatin resistance (2012, background): “Moreover, it has been shown that cisplatin resistance can develop in initially cisplatinsensitive tumors because of secondary mutations that compensate for BRCA1/2 deficiency and re-establish HR (Edwards et al., 2008; Sakai et al., 2008).”
Tumor heterogeneity: causes and consequences (2009, background): “These tumors are deficient in homologous recombination-mediated DNA repair (HRR), which increases their genomic instability but makes them highly sensitive to platinum compounds and PARP (poly ADP ribose polymerase) inhibitors.”
Synthetic lethal targeting of PTEN mutant cells with PARP inhibitors (2009, methodology): “PARP inhibitors KU0058948 (Farmer et al, 2005) and KU0059436 (Evers et al, 2008; Fong et al, 2008) (KuDOS Pharmaceuticals/Astra Zeneca), cisplatin and paclitaxel (Sigma–Aldrich) were used as described previously (Edwards et al, 2008; Farmer et al, 2005).”
Patterns of genomic loss of heterozygosity predict homologous recombination repair defects in epithelial ovarian cancer (2012, background): “Published studies have demonstrated that secondary reversion mutations that restore BRCA2 function can arise in BRCA2 mutant cell lines after exposure to platinum agents (Edwards et al, 2008; Sakai et al, 2008, 2009).”
MMEJ repair of double-strand breaks (director’s cut): deleted sequences and alternative endings (2008, background): “Furthermore, a more complete understanding of the cellular contexts which favor MMEJ might serve to improve cancer treatments, as demonstrated by the potential role of MMEJ in chemotherapy-induced brca2 mutation reversion [ 78 ,79].”
Homologous recombination and human health: the roles of BRCA1, BRCA2 and associated proteins (2015, background): “2011); in fact, deletion of the DBD is one type of reversion mutation identified for BRCA2 (Edwards et al. 2008).”
How the fanconi anemia pathway guards the genome. (2009, background): “The downside, however, is that, probably owing to their lower accuracy of DNA repair, these cells accumulate secondary intragenic modifications that can lead to reversal of the BRCA2 mutation, allowing these cells to acquire crosslink resistance (43, 123).”
Homologous recombination and its regulation (2012, background): “In addition, BRCA2-deficient cells were shown to gain resistance to PARP inhibitors due to acquired mutations in BRCA2 that restore its activity (317,318).”
Machine learning approaches to drug response prediction: challenges and recent progress (2020, background): “Studies have shown that treatment with cisplatin, a DNA damaging agent usually effective against BRCA de ﬁ cient cancers, can lead to mutations restoring BRCA function and subsequently the activity of the Homologous Repair (HR) pathway 55,56 .”