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Nicola J. Curtin
Newcastle University
DNA repairPoly ADP ribose polymeraseCancer researchMedicineBiology
304Publications
57H-index
13.8kCitations
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Publications 293
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#1Hannah L. Smith (Newcastle University)H-Index: 1
#2Harriet E. D. Southgate (Newcastle University)
Last. Nicola J. Curtin (Newcastle University)H-Index: 57
view all 4 authors...
DNA damage response (DDR) pathway prevents high level endogenous and environmental DNA damage being replicated and passed on to the next generation of cells via an orchestrated and integrated network of cell cycle checkpoint signalling and DNA repair pathways. Depending on the type of damage, and where in the cell cycle it occurs different pathways are involved, with the ATM-CHK2-p53 pathway controlling the G1 checkpoint or ATR-CHK1-Wee1 pathway controlling the S and G2/M checkpoints. Loss of G1...
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#1Nicola J. Curtin (Newcastle University)H-Index: 57
#2Krisztián BányaiH-Index: 1
Last. Péter Bai (University of Debrecen)H-Index: 27
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: Clinically approved PARP inhibitors (PARPi) have a mild adverse effect profile and are well-tolerated as continuous daily oral therapy. We review the evidence that justifies the repurposing of PARPi to block the proliferation of SARS-CoV-2 and combat the life-threatening sequelae of COVID-19 by several mechanisms. PARPi's can effectively decrease IL-6, IL-1 and TNFα levels (key interleukins in SARS-CoV-2-induced cytokine storm) and can alleviate subsequent lung fibrosis, as demonstrated in mur...
1 CitationsSource
#1Harriet E. D. Southgate (Newcastle University)
#2Lindi Chen (Newcastle University)H-Index: 7
Last. Nicola J. Curtin (Newcastle University)H-Index: 57
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Background: High risk neuroblastoma (HR-NB) is one the most difficult childhood cancers to cure. These tumours frequently present with DNA damage response (DDR) defects including loss or mutation of key DDR genes, oncogene-induced replication stress (RS) and cell cycle checkpoint dysfunction. Aim: To identify biomarkers of sensitivity to inhibition of Ataxia telangiectasia and Rad3 related (ATR), a DNA damage sensor, and poly (ADP-ribose) polymerase (PARP), which is required for single strand br...
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#1Hannah L. Smith (Newcastle University)H-Index: 1
#2Lisa Prendergast (Newcastle University)H-Index: 5
Last. Nicola J. Curtin (Newcastle University)H-Index: 57
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PARP inhibition results in the accumulation of DNA SSBs, causing replication stress (RS) and lesions that can only be resolved by homologous recombination repair (HRR). Defects in HRR, e.g., due to BRCA2 mutation, confer profound sensitivity to PARP inhibitor (PARPi) cytotoxicity. In response to RS, CHK1 is activated to signal to S and G2/M cell cycle checkpoints and also to HRR. To determine the relative contribution of these two functions of CHK1 to survival following PARPi exposure, we invest...
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#1Harriet E. D. Southgate (Newcastle University)
#2Lindi Chen (Newcastle University)H-Index: 7
Last. Deborah A. Tweddle (Newcastle University)H-Index: 23
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Despite intensive multimodal therapy, the survival rate for high risk neuroblastoma (HR-NB) remains less than 50%. Most cases initially respond to treatment but almost half will subsequently relapse with aggressive treatment resistant disease. Novel treatments exploiting the molecular pathology of NB and/or overcoming resistance to current genotoxic therapies are needed before survival rates can significantly improve. DNA damage response (DDR) defects are frequently observed in HR-NB including a...
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#1Alice Bradbury (Newcastle University)H-Index: 2
#2Sally Hall (Newcastle University)H-Index: 2
Last. Yvette Drew (Newcastle University)H-Index: 15
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Abstract The DNA damage response (DDR) machinery is responsible for detecting DNA damage, pausing the cell cycle and initiating DNA repair. Ataxia telangiectasia and Rad3-related (ATR) protein is a key kinase at the heart of the DDR, responsible for sensing replication stress (RS) and signalling it to S and G2/M checkpoints to facilitate repair. In cancer, loss of G1 checkpoint control and activation of oncogenes that drive replication, result in cancer cells more likely to enter S phase with in...
4 CitationsSource
#1Nicola J. Curtin (Newcastle University)H-Index: 57
The poly(ADP-ribose) polymerase (PARP) inhibitor, Rubraca®, was given its first accelerated approval for BRCA-mutated ovarian cancer by the FDA at the end of 2016, and further approval by the FDA, EMA and NICE followed. Scientists at Newcastle University initiated the early stages, and several collaborations with scientists in academia and the pharmaceutical industry enabled its final development to the approval stage. Although originally considered as a chemo- or radiosensitiser, its current ap...
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#1A.J. Chalmers (Glas.: University of Glasgow)H-Index: 1
#2C. S. K. Chan (National Cancer Research Institute)H-Index: 2
Last. Carolyn ChanH-Index: 1
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1 CitationsSource
#1Nicola J. Curtin (Newcastle University)H-Index: 57
#2Yvette Drew (Newcastle University)H-Index: 15
Last. Sweta Sharma-Saha (Newcastle University)H-Index: 1
view all 3 authors...
BRCA1/2 mutations and poly (ADP-ribose) polymerase (PARP) inhibitors are paradigmatic of synthetic lethal therapy. However, the activity of PARP inhibitors seems to vary considerably across BRCA1/2-mutant cancers and new insights into the tumour-lineage dependency of this synthetic lethal relationship might explain why BRCA1/2 mutations are not tumour-agnostic biomarkers of a response to PARP inhibitors.
2 CitationsSource
#1Lucy Gentles (Newcastle University)H-Index: 1
#2S Sharma Saha (Newcastle University)
Last. Rachel O'Donnell (Newcastle University)H-Index: 6
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Introduction/Background In the phase III LACC cervical cancer trial, shorter disease-free survival and overall survival was observed in patients treated with minimally invasive radical hysterectomy in comparison to traditional open surgery. One hypothesis for this difference is an adverse effect of the prolonged exposure to the hypoxic, CO2-rich, acidotic environment created during minimally invasive surgery. Greater cervical tumour hypoxia-inducible factor 1α (HIF-1α) indicating tissue hypoxia ...
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