Now showing items 1-20 of 28

    • A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations. 

      George, SL; Izquierdo, E; Campbell, J; Koutroumanidou, E; Proszek, P; Jamal, S; Hughes, D; Yuan, L; Marshall, LV; Carceller, F; Chisholm, JC; Vaidya, S; Mandeville, H; Angelini, P; Wasti, A; Bexelius, T; Thway, K; Gatz, SA; Clarke, M; Al-Lazikani, B; Barone, G; Anderson, J; Tweddle, DA; Gonzalez, D; Walker, BA; Barton, J; Depani, S; Eze, J; Ahmed, SW; Moreno, L; Pearson, A; Shipley, J; Jones, C; Hargrave, D; Jacques, TS; Hubank, M; Chesler, L (2019-11)
      BACKGROUND:For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. METHODS:We have developed a hybrid-capture next-generation ...
    • An <i>In Vivo</i> Functional Screen Identifies JNK Signaling As a Modulator of Chemotherapeutic Response in Breast Cancer. 

      Ashenden, M; van Weverwijk, A; Murugaesu, N; Fearns, A; Campbell, J; Gao, Q; Iravani, M; Isacke, CM (2017-09)
      Chemotherapy remains the mainstay of treatment for advanced breast cancer; however, resistance is an inevitable event for the majority of patients with metastatic disease. Moreover, there is little information available ...
    • ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. 

      Williamson, CT; Miller, R; Pemberton, HN; Jones, SE; Campbell, J; Konde, A; Badham, N; Rafiq, R; Brough, R; Gulati, A; Ryan, CJ; Francis, J; Vermulen, PB; Reynolds, AR; Reaper, PM; Pollard, JR; Ashworth, A; Lord, CJ (2016-12-13)
      Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
    • ATR Is a Therapeutic Target in Synovial Sarcoma. 

      Jones, SE; Fleuren, EDG; Frankum, J; Konde, A; Williamson, CT; Krastev, DB; Pemberton, HN; Campbell, J; Gulati, A; Elliott, R; Menon, M; Selfe, JL; Brough, R; Pettitt, SJ; Niedzwiedz, W; van der Graaf, WTA; Shipley, J; Ashworth, A; Lord, CJ (2017-12)
      Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by expression of SS18-SSX fusions, where treatment options are limited. To identify therapeutically actionable genetic dependencies in SS, we ...
    • CancerGD: a resource for identifying and interpreting genetic dependencies in cancer 

      Bridgett, S; Campbell, J; Lord, C; Ryan, C (2016-10-26)
      Abstract Genes whose function is selectively essential in the presence of cancer associated genetic aberrations represent promising targets for the development of precision therapeutics. Here we present CancerGD ( ...
    • CancerGD: A Resource for Identifying and Interpreting Genetic Dependencies in Cancer. 

      Bridgett, S; Campbell, J; Lord, CJ; Ryan, CJ (2017-07-12)
      Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ...
    • canSAR: update to the cancer translational research and drug discovery knowledgebase. 

      Mitsopoulos, C; Di Micco, P; Fernandez, EV; Dolciami, D; Holt, E; Mica, IL; Coker, EA; Tym, JE; Campbell, J; Che, KH; Ozer, B; Kannas, C; Antolin, AA; Workman, P; Al-Lazikani, B (2021-01)
      canSAR (http://cansar.icr.ac.uk) is the largest, public, freely available, integrative translational research and drug discovery knowledgebase for oncology. canSAR integrates vast multidisciplinary data from across genomic, ...
    • CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
      Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
    • Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. 

      Holme, H; Gulati, A; Brough, R; Fleuren, EDG; Bajrami, I; Campbell, J; Chong, IY; Costa-Cabral, S; Elliott, R; Fenton, T; Frankum, J; Jones, SE; Menon, M; Miller, R; Pemberton, HN; Postel-Vinay, S; Rafiq, R; Selfe, JL; von Kriegsheim, A; Munoz, AG; Rodriguez, J; Shipley, J; van der Graaf, WTA; Williamson, CT; Ryan, CJ; Pettitt, S; Ashworth, A; Strauss, SJ; Lord, CJ (2018-07-13)
      Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...
    • Correction: CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
    • Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. 

      Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; Stoynov, SS; Ashworth, A; Lord, CJ (2018-05-22)
      Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...
    • E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. 

      Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; Frankum, J; Song, F; Rafiq, R; Konde, A; Krastev, DB; Menon, M; Campbell, J; Gulati, A; Kumar, R; Pettitt, SJ; Gurden, MD; Cardenosa, ML; Chong, I; Gazinska, P; Wallberg, F; Sawyer, EJ; Martin, L-A; Dowsett, M; Linardopoulos, S; Natrajan, R; Ryan, CJ; Derksen, PWB; Jonkers, J; Tutt, ANJ; Ashworth, A; Lord, CJ (2018-04)
      The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...
    • Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. 

      Nikkilä, J; Kumar, R; Campbell, J; Brandsma, I; Pemberton, HN; Wallberg, F; Nagy, K; Scheer, I; Vertessy, BG; Serebrenik, AA; Monni, V; Harris, RS; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-06)
      Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 status on ...
    • Evaluation of CDK12 Protein Expression as a Potential Novel Biomarker for DNA Damage Response-Targeted Therapies in Breast Cancer. 

      Naidoo, K; Wai, PT; Maguire, SL; Daley, F; Haider, S; Kriplani, D; Campbell, J; Mirza, H; Grigoriadis, A; Tutt, A; Moseley, PM; Abdel-Fatah, TMA; Chan, SYT; Madhusudan, S; Rhaka, EA; Ellis, IO; Lord, CJ; Yuan, Y; Green, AR; Natrajan, R (2018-01)
      Disruption of Cyclin-Dependent Kinase 12 (<i>CDK12</i>) is known to lead to defects in DNA repair and sensitivity to platinum salts and PARP1/2 inhibitors. However, <i>CDK12</i> has also been proposed as an oncogene in ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells. 

      Pettitt, SJ; Krastev, DB; Pemberton, HN; Fontebasso, Y; Frankum, J; Rehman, FL; Brough, R; Song, F; Bajrami, I; Rafiq, R; Wallberg, F; Kozarewa, I; Fenwick, K; Armisen-Garrido, J; Swain, A; Gulati, A; Campbell, J; Ashworth, A; Lord, CJ (2017-03)
      We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ...
    • Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress. 

      McDade, SS; Patel, D; Moran, M; Campbell, J; Fenwick, K; Kozarewa, I; Orr, NJ; Lord, CJ; Ashworth, AA; McCance, DJ (2014-06)
      In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by ...
    • High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial. 

      Pearson, A; Smyth, E; Babina, IS; Herrera-Abreu, MT; Tarazona, N; Peckitt, C; Kilgour, E; Smith, NR; Geh, C; Rooney, C; Cutts, R; Campbell, J; Ning, J; Fenwick, K; Swain, A; Brown, G; Chua, S; Thomas, A; Johnston, SRD; Ajaz, M; Sumpter, K; Gillbanks, A; Watkins, D; Chau, I; Popat, S; Cunningham, D; Turner, NC (2016-08)
      Unlabelled FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level ...
    • <i>In Vivo</i> Modeling of Chemoresistant Neuroblastoma Provides New Insights into Chemorefractory Disease and Metastasis. 

      Yogev, O; Almeida, GS; Barker, KT; George, SL; Kwok, C; Campbell, J; Zarowiecki, M; Kleftogiannis, D; Smith, LM; Hallsworth, A; Berry, P; Möcklinghoff, T; Webber, HT; Danielson, LS; Buttery, B; Calton, EA; da Costa, BM; Poon, E; Jamin, Y; Lise, S; Veal, GJ; Sebire, N; Robinson, SP; Anderson, J; Chesler, L (2019-10)
      Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant <i>in vivo</i> models has limited our insight into the ...
    • Identification of highly penetrant Rb-related synthetic lethal interactions in triple negative breast cancer. 

      Brough, R; Gulati, A; Haider, S; Kumar, R; Campbell, J; Knudsen, E; Pettitt, SJ; Ryan, CJ; Lord, CJ (2018-10)
      Although defects in the RB1 tumour suppressor are one of the more common driver alterations found in triple-negative breast cancer (TNBC), therapeutic approaches that exploit this have not been identified. By integrating ...