Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy

By H. Farmer, N. Mccabe, C. Lord, Andrew Tutt, Damian A. Johnson, T. Richardson, M. Santarosa, Krystyna J. Dillon, Ian D. Hickson, C. Knights and 4 more. Nature, 2005

6,462 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/5ba510b9309e5cc564d386f886cd5a5e2b82c50f

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Citations in the corpus

Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase (2005, background): “This is also supported by sensitivity of both BRCA1 -/- and BRCA2 -/- embryonic stem (ES) cells to the PARP inhibitors KU0058684 and KU0058948 (ref”
Triple-negative breast cancer: disease entity or title of convenience? (2010, background): “Loss of BRCA1 or BRCA2 is thought to lead to increased dependence on PARP for DNA repair, and preclinical data indicate that BRCA1 and BRCA2 defective cells are markedly sensitive to PARP inhibitors”
PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways (2006, background): “However, this distinction of severity between SSBs and DSBs may be altered during S phase, where SSBs can be converted to one-ended DSBs which, if not repaired by HRR, can have serious consequences for the cell (28,29).”
DNA double-strand break repair: from mechanistic understanding to cancer treatment. (2007, background): “Two recent studies have indeed found that BRCA1 or BRCA2 deficiency leads to a dramatic hypersensitivity to PARP inhibitors, raising hopes for developing a powerful, targeted therapy for these tumors [85,131].”
Homologous recombination and its regulation (2012, background): “One main concept in devising these strategies is that HR-deficient tumours are more sensitive to killing by DNA damaging agents or by chemicals that inhibit other repair pathways or checkpoint mechanisms (208,307,308).”
Cell cycle, CDKs and cancer: a changing paradigm (2009, background): “For instance, BRCA1 or BRCA2 dysfunction resulting in deficient homologous recombination repair sensitizes tumour cells to the inhibition of poly(ADP-ribose) polymerase (PARP), a protein involved in base excision repai”
HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational-signatures (2017, background): “Twelve consensus base-substitution signatures were identified previously in the 560 breast whole genomes: signatures 1, 2, 3, 5, 6, 8, 13, 17, 18, 20, 26 and 30.”
Ovarian carcinomas: five distinct diseases with different origins, genetic alterations, and clinicopathological features (2012, methodology): “PARP inhibitors that target loss of BRCA function and inability to repair double-strand breaks in DNA have been used [40, 41].”
DNA repair pathways as targets for cancer therapy (2008, background): “gov/cancertopics/types/breast">breast and ovarian cancers that lack wild-type copies of the BRCA1 or BRCA2 gene”
Principles of Cancer Therapy: Oncogene and Non-oncogene Addiction (2009, positive): “Furthermore, these tumors rely heavily on other forms of DNA repair such as base-excision repair, resulting in sensitivity to inhibitors of poly-ADP-ribose polymerase (PARP1), an enzyme that facilitates repair of singlestranded breaks (Bryant et al., 2005; Farmer et al., 2005).”