Peter Stephens
Newcastle University
CancerDNA repairCancer researchRadiation therapyMedicine
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Publications 15
#2Divyanshu DuaH-Index: 2
Last. Debashis Sarker (University of Cambridge)H-Index: 18
view all 11 authors...
2505Background: A phase I study was done to establish the safety, MTD and anti-tumour efficacy of the novel PARP 1/2 and Tankyrase 1/2 inhibitor, 2X-121 (E7449). A novel tumor agnostic molecular bi...
#1Nouf Alsubhi (University of Nottingham)H-Index: 4
#2Fiona K. Middleton (Newcastle University)H-Index: 6
Last. Srinivasan Madhusudan (University of Nottingham)H-Index: 32
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Abstract Radiation-induced DNA damage activates the DNA damage response (DDR). DDR up-regulation may predict radio-resistance and increase the risk of early local recurrence despite radiotherapy in early stage breast cancers. In 1755 early stage breast cancers, DDR signalling [ATM, ATR, total Ckh1, Chk1 phosphorylated at serine 345 (pChk1), Chk2, p53], base excision repair [PARP1, POLβ, XRCC1, FEN1, SMUG1], non-homologous end joining (Ku70/Ku80, DNA-PKcs) and homologous recombination [RAD51, BRC...
12 CitationsSource
#1Andrew J. MasseyH-Index: 1
#2Peter Stephens (Newcastle University)H-Index: 5
Last. Nicola J. Curtin (Newcastle University)H-Index: 56
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Abstract Background Chk1 inhibitors are currently under clinical evaluation as single agents and in combination with cytotoxic chemotherapy. Understanding determinants of sensitivity and novel combinations is critical for further clinical development. Methods Potentiation of mTOR inhibitor cytotoxicity by the Chk1 inhibitor V158411 was determined in p53 mutant colon cancer cells. DNA damage response, expression levels of repair proteins, cell cycle effects and the contribution of alternative DSB...
11 CitationsSource
#1Ruth Plummer (Newcastle University)H-Index: 30
#2D. Dua (Freeman Hospital)H-Index: 1
Last. D Sarker (St Thomas' Hospital)H-Index: 1
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2 CitationsSource
#1Ruth PlummerH-Index: 30
#2Peter StephensH-Index: 5
Last. Mario CamponeH-Index: 58
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Purpose Poly(ADP-ribose) polymerase-1 (PARP-1) is a nuclear enzyme important in DNA repair. PARP-1 activation at points of DNA strand break results in poly(ADP-ribose) polymer formation, opening the DNA structure, and allowing access of other repair enzymes. CEP-9722 inhibits PARP-1 and PARP-2 and is designed to potentiate DNA-damaging chemotherapies.
22 CitationsSource
#1Ruth Plummer (Freeman Hospital)H-Index: 30
#2Divyanshu Dua (St Thomas' Hospital)H-Index: 2
Last. Debashis Sarker (Guy's and St Thomas' NHS Foundation Trust)H-Index: 18
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e19531^ Background: E7449 is an orally bioavailable, likely brain penetrable, potent small-molecule inhibitor of poly (ADP-ribose) polymerase (PARP) 1 and PARP 2 with an IC50 of 1.0 and 1.2 nmol/L respectively. E7449 is a poor P-gp substrate. Preclinically, E7449 potentiates the antitumor activity of chemotherapy and radiotherapy and has activity as a single-agent in BRCA-deficient and other tumors. A Phase 1 study of E7449 as a single agent is underway to determine the MTD, safety, PK, PD, prel...
1 CitationsSource
#1Peter StephensH-Index: 5
#2Ruth PlummerH-Index: 30
#1Christophe MassardH-Index: 43
#2J MargettsH-Index: 1
Last. Ruth PlummerH-Index: 30
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#1Christophe MassardH-Index: 43
#2J MargettsH-Index: 1
Last. Ruth PlummerH-Index: 30
view all 15 authors...