Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase

By H. Bryant, N. Schultz, H. Thomas, Kayan M. Parker, Dan Flower, Elena Lopez, S. Kyle, M. Meuth, N. Curtin, Thomas Helleday. Nature, 2005

4,680 citations recorded by the source corpus.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/a2548ef6dc03583937cf7bf2eb7b615a17f377cc

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Citations in the corpus

Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers. (2009, neutral): “Grade 1−2 0 2 (50) 0 2 (10) 1 ( 12 ) 3 (60) 8 (13)”
PARP Inhibitors: Clinical Relevance, Mechanisms of Action and Tumor Resistance (2020, background): “Therefore, it was initially hypothesized that PARP inhibitors may induce lethality by impairing the repair of DNA single-strand breaks and leading to the accumulation of damage (Bryant et al., 2005).”
Detecting treatment response in a model of human breast adenocarcinoma using hyperpolarised [1-13C]pyruvate and [1,4-13C2]fumarate (2010, background): “…fumarate; DNP There has been substantial growth and investment in drug discovery and development programmes in oncology in recent years, with the aim of producing therapeutics targeted at the spectrum of genetic abnormalities found in cancer (Hu et al, 2000; Semenza, 2003; Bryant et al, 2005).”
Homologous recombination deficiency: Exploiting the fundamental vulnerability of ovarian cancer (2015, background): “This mechanism may explain the cytotoxic effect of certain drug combinations, such as PARPi and temozolomide or topotecan (95–97), and is believed to account for the observation that PARP1 knockdown selectively kills HRdeficient cells (18, 75, 82), as these PARP-trapping–induced DNA lesions are thou”
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).”
RIF1 Is Essential for 53BP1-Dependent Nonhomologous End Joining and Suppression of DNA Double-Strand Break Resection (2013, background): “BRCA1-deficient cells are hypersensitive to poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi), which trigger the formation of replication-associated DNA damage that requires HR for its resolution (Bryant et al., 2005; Farmer et al., 2005; Helleday, 2011).”
Poly(ADP-ribosyl)ation by PARP-1: 'PAR-laying' NAD+ into a nuclear signal. (2005, background): “Furthermore, BRCA1- or BRCA2-deficient cells treated with a PARP-1 inhibitor show major mitotic chromosome aberrations and a loss of formation of RAD51 foci, suggesting defects in DSB repair involving RAD51-dependent homologous recombination (Bryant et al. 2005; Farmer et al. 2005).”
The underlying mechanism for the PARP and BRCA synthetic lethality: Clearing up the misunderstandings (2011, background): “Here, it is worth mentioning that BRCA defective cells are far more sensitive to PARP inhibitors than to siRNA knockdown of PARP-1 (Bryant et al., 2005; Farmer et al., 2005).”