Now showing items 1-20 of 23

    • 3D Functional Genomics Screens Identify CREBBP as a Targetable Driver in Aggressive Triple-Negative Breast Cancer. 

      Peck, B; Bland, P; Mavrommati, I; Muirhead, G; Cottom, H; Wai, PT; Maguire, SL; Barker, HE; Morrison, E; Kriplani, D; Yu, L; Gibson, A; Falgari, G; Brennan, K; Farnie, G; Buus, R; Marlow, R; Novo, D; Knight, E; Guppy, N; Kolarevic, D; Susnjar, S; Milijic, NM; Naidoo, K; Gazinska, P; Roxanis, I; Pancholi, S; Martin, L-A; Holgersen, EM; Cheang, MCU; Noor, F; Postel-Vinay, S; Quinn, G; McDade, S; Krasny, L; Huang, P; Daley, F; Wallberg, F; Choudhary, JS; Haider, S; Tutt, AN; Natrajan, R (2021-01-28)
      Triple-negative breast cancers (TNBC) are resistant to standard-of-care chemotherapy and lack known targetable driver gene alterations. Identification of novel drivers could aid the discovery of new treatment strategies ...
    • ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile. 

      Favara, DM; Zois, CE; Haider, S; Pires, E; Sheldon, H; McCullagh, J; Banham, AH; Harris, AL (2019-11-25)
      Adhesion G Protein-Coupled Receptor L4 (ADGRL4/ELTD1) is an endothelial cell adhesion G protein-coupled receptor (aGPCR) which regulates physiological and tumour angiogenesis, providing an attractive target for anti-cancer ...
    • Capture Hi-C identifies putative target genes at 33 breast cancer risk loci. 

      Baxter, JS; Leavy, OC; Dryden, NH; Maguire, S; Johnson, N; Fedele, V; Simigdala, N; Martin, L-A; Andrews, S; Wingett, SW; Assiotis, I; Fenwick, K; Chauhan, R; Rust, AG; Orr, N; Dudbridge, F; Haider, S; Fletcher, O (2018-03-12)
      Genome-wide association studies (GWAS) have identified approximately 100 breast cancer risk loci. Translating these findings into a greater understanding of the mechanisms that influence disease risk requires identification ...
    • Clinical <i>BRCA1/2</i> Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance. 

      Pettitt, SJ; Frankum, JR; Punta, M; Lise, S; Alexander, J; Chen, Y; Yap, TA; Haider, S; Tutt, ANJ; Lord, CJ (2020-10)
      Reversion mutations in <i>BRCA1</i> or <i>BRCA2</i> are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 ...
    • Combining BRAF inhibition with oncolytic herpes simplex virus enhances the immune-mediated antitumor therapy of BRAF-mutant thyroid cancer. 

      Crespo-Rodriguez, E; Bergerhoff, K; Bozhanova, G; Foo, S; Patin, EC; Whittock, H; Buus, R; Haider, S; Muirhead, G; Thway, K; Newbold, K; Coffin, RS; Vile, RG; Kim, D; McLaughlin, M; Melcher, AA; Harrington, KJ; Pedersen, M (2020-08)
      Background The aggressive clinical behavior of poorly differentiated and anaplastic thyroid cancers (PDTC and ATC) has proven challenging to treat, and survival beyond a few months from diagnosis is rare. Although 30%-60% ...
    • 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 ...
    • Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element. 

      Baxter, JS; Johnson, N; Tomczyk, K; Gillespie, A; Maguire, S; Brough, R; Fachal, L; Michailidou, K; Bolla, MK; Wang, Q; Dennis, J; Ahearn, TU; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Arndt, V; Aronson, KJ; Augustinsson, A; Becher, H; Beckmann, MW; Behrens, S; Benitez, J; Bermisheva, M; Bogdanova, NV; Bojesen, SE; Brenner, H; Brucker, SY; Cai, Q; Campa, D; Canzian, F; Castelao, JE; Chan, TL; Chang-Claude, J; Chanock, SJ; Chenevix-Trench, G; Choi, J-Y; Clarke, CL; NBCS Collaborators; Colonna, S; Conroy, DM; Couch, FJ; Cox, A; Cross, SS; Czene, K; Daly, MB; Devilee, P; Dörk, T; Dossus, L; Dwek, M; Eccles, DM; Ekici, AB; Eliassen, AH; Engel, C; Fasching, PA; Figueroa, J; Flyger, H; Gago-Dominguez, M; Gao, C; García-Closas, M; García-Sáenz, JA; Ghoussaini, M; Giles, GG; Goldberg, MS; González-Neira, A; Guénel, P; Gündert, M; Haeberle, L; Hahnen, E; Haiman, CA; Hall, P; Hamann, U; Hartman, M; Hatse, S; Hauke, J; Hollestelle, A; Hoppe, R; Hopper, JL; Hou, M-F; kConFab Investigators; ABCTB Investigators; Ito, H; Iwasaki, M; Jager, A; Jakubowska, A; Janni, W; John, EM; Joseph, V; Jung, A; Kaaks, R; Kang, D; Keeman, R; Khusnutdinova, E; Kim, S-W; Kosma, V-M; Kraft, P; Kristensen, VN; Kubelka-Sabit, K; Kurian, AW; Kwong, A; Lacey, JV; Lambrechts, D; Larson, NL; Larsson, SC; Le Marchand, L; Lejbkowicz, F; Li, J; Long, J; Lophatananon, A; Lubiński, J; Mannermaa, A; Manoochehri, M; Manoukian, S; Margolin, S; Matsuo, K; Mavroudis, D; Mayes, R; Menon, U; Milne, RL; Mohd Taib, NA; Muir, K; Muranen, TA; Murphy, RA; Nevanlinna, H; O'Brien, KM; Offit, K; Olson, JE; Olsson, H; Park, SK; Park-Simon, T-W; Patel, AV; Peterlongo, P; Peto, J; Plaseska-Karanfilska, D; Presneau, N; Pylkäs, K; Rack, B; Rennert, G; Romero, A; Ruebner, M; Rüdiger, T; Saloustros, E; Sandler, DP; Sawyer, EJ; Schmidt, MK; Schmutzler, RK; Schneeweiss, A; Schoemaker, MJ; Shah, M; Shen, C-Y; Shu, X-O; Simard, J; Southey, MC; Stone, J; Surowy, H; Swerdlow, AJ; Tamimi, RM; Tapper, WJ; Taylor, JA; Teo, SH; Teras, LR; Terry, MB; Toland, AE; Tomlinson, I; Truong, T; Tseng, C-C; Untch, M; Vachon, CM; van den Ouweland, AMW; Wang, SS; Weinberg, CR; Wendt, C; Winham, SJ; Winqvist, R; Wolk, A; Wu, AH; Yamaji, T; Zheng, W; Ziogas, A; Pharoah, PDP; Dunning, AM; Easton, DF; Pettitt, SJ; Lord, CJ; Haider, S; Orr, N; Fletcher, O
      A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), ...
    • Hypoxia-induced switch in SNAT2/SLC38A2 regulation generates endocrine resistance in breast cancer. 

      Morotti, M; Bridges, E; Valli, A; Choudhry, H; Sheldon, H; Wigfield, S; Gray, N; Zois, CE; Grimm, F; Jones, D; Teoh, EJ; Cheng, W-C; Lord, S; Anastasiou, D; Haider, S; McIntyre, A; Goberdhan, DCI; Buffa, F; Harris, AL
      Tumor hypoxia is associated with poor patient outcomes in estrogen receptor-α-positive (ERα<sup>+</sup>) breast cancer. Hypoxia is known to affect tumor growth by reprogramming metabolism and regulating amino acid (AA) ...
    • 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 ...
    • IGF-1R associates with adverse outcomes after radical radiotherapy for prostate cancer. 

      Aleksic, T; Verrill, C; Bryant, RJ; Han, C; Worrall, AR; Brureau, L; Larré, S; Higgins, GS; Fazal, F; Sabbagh, A; Haider, S; Buffa, FM; Cole, D; Macaulay, VM
      Background Activated type 1 insulin-like growth factor receptors (IGF-1Rs) undergo internalisation and nuclear translocation, promoting cell survival. We previously reported that IGF-1R inhibition delays DNA damage repair, ...
    • Impairment of a distinct cancer-associated fibroblast population limits tumour growth and metastasis. 

      Jungwirth, U; van Weverwijk, A; Evans, RJ; Jenkins, L; Vicente, D; Alexander, J; Gao, Q; Haider, S; Iravani, M; Isacke, CM (2021-06-10)
      Profiling studies have revealed considerable phenotypic heterogeneity in cancer-associated fibroblasts (CAFs) present within the tumour microenvironment, however, functional characterisation of different CAF subsets is ...
    • Integrated Pharmacodynamic Analysis Identifies Two Metabolic Adaption Pathways to Metformin in Breast Cancer. 

      Lord, SR; Cheng, W-C; Liu, D; Gaude, E; Haider, S; Metcalf, T; Patel, N; Teoh, EJ; Gleeson, F; Bradley, K; Wigfield, S; Zois, C; McGowan, DR; Ah-See, M-L; Thompson, AM; Sharma, A; Bidaut, L; Pollak, M; Roy, PG; Karpe, F; James, T; English, R; Adams, RF; Campo, L; Ayers, L; Snell, C; Roxanis, I; Frezza, C; Fenwick, JD; Buffa, FM; Harris, AL
      Late-phase clinical trials investigating metformin as a cancer therapy are underway. However, there remains controversy as to the mode of action of metformin in tumors at clinical doses. We conducted a clinical study ...
    • Landscape of transcriptomic interactions between breast cancer and its microenvironment. 

      Fox, NS; Haider, S; Harris, AL; Boutros, PC (2019-07-15)
      Solid tumours comprise mixtures of tumour cells (TCs) and tumour-adjacent cells (TACs), and the intricate interconnections between these diverse populations shape the tumour's microenvironment. Despite this complexity, ...
    • Pan-cancer analysis of whole genomes. 

      ICGC/TCGA Pan-Cancer Analysis of Whole Genomes Consortium (2020-02-05)
      Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale<sup>1-3</sup>. Here we report the integrative analysis ...
    • PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer. 

      Chabanon, RM; Muirhead, G; Krastev, DB; Adam, J; Morel, D; Garrido, M; Lamb, A; Hénon, C; Dorvault, N; Rouanne, M; Marlow, R; Bajrami, I; Cardeñosa, ML; Konde, A; Besse, B; Ashworth, A; Pettitt, SJ; Haider, S; Marabelle, A; Tutt, AN; Soria, J-C; Lord, CJ; Postel-Vinay, S (2019-03)
      The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA ...
    • Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance. 

      Zatreanu, D; Robinson, HMR; Alkhatib, O; Boursier, M; Finch, H; Geo, L; Grande, D; Grinkevich, V; Heald, RA; Langdon, S; Majithiya, J; McWhirter, C; Martin, NMB; Moore, S; Neves, J; Rajendra, E; Ranzani, M; Schaedler, T; Stockley, M; Wiggins, K; Brough, R; Sridhar, S; Gulati, A; Shao, N; Badder, LM; Novo, D; Knight, EG; Marlow, R; Haider, S; Callen, E; Hewitt, G; Schimmel, J; Prevo, R; Alli, C; Ferdinand, A; Bell, C; Blencowe, P; Bot, C; Calder, M; Charles, M; Curry, J; Ekwuru, T; Ewings, K; Krajewski, W; MacDonald, E; McCarron, H; Pang, L; Pedder, C; Rigoreau, L; Swarbrick, M; Wheatley, E; Willis, S; Wong, AC; Nussenzweig, A; Tijsterman, M; Tutt, A; Boulton, SJ; Higgins, GS; Pettitt, SJ; Smith, GCM; Lord, CJ (2021-06-17)
      To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ...
    • Quantitative Assessment and Prognostic Associations of the Immune Landscape in Ovarian Clear Cell Carcinoma. 

      Khalique, S; Nash, S; Mansfield, D; Wampfler, J; Attygale, A; Vroobel, K; Kemp, H; Buus, R; Cottom, H; Roxanis, I; Jones, T; von Loga, K; Begum, D; Guppy, N; Ramagiri, P; Fenwick, K; Matthews, N; Hubank, MJF; Lord, CJ; Haider, S; Melcher, A; Banerjee, S; Natrajan, R (2021-07-30)
      Ovarian clear cell carcinoma (OCCC) is a rare subtype of epithelial ovarian cancer characterised by a high frequency of loss-of-function <i>ARID1A</i> mutations and a poor response to chemotherapy. Despite their generally ...
    • Real-time ex vivo perfusion of human lymph nodes invaded by cancer (REPLICANT): a feasibility study. 

      Barrow-McGee, R; Procter, J; Owen, J; Woodman, N; Lombardelli, C; Kothari, A; Kovacs, T; Douek, M; George, S; Barry, PA; Ramsey, K; Gibson, A; Buus, R; Holgersen, E; Natrajan, R; Haider, S; Shattock, MJ; Gillett, C; Tutt, AN; Pinder, SE; Naidoo, K (2020-03)
      Understanding how breast cancer (BC) grows in axillary lymph nodes (ALNs), and refining how therapies might halt that process, is clinically important. However, modelling the complex ALN microenvironment is difficult, and ...
    • Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency. 

      Bajrami, I; Walker, C; Krastev, DB; Weekes, D; Song, F; Wicks, AJ; Alexander, J; Haider, S; Brough, R; Pettitt, SJ; Tutt, ANJ; Lord, CJ (2021-11-08)
      PARP enzymes utilise NAD+ as a co-substrate for their enzymatic activity. Inhibition of PARP1 is synthetic lethal with defects in either BRCA1 or BRCA2. In order to assess whether other genes implicated in NAD+ metabolism ...
    • SOX11 promotes invasive growth and ductal carcinoma in situ progression. 

      Oliemuller, E; Kogata, N; Bland, P; Kriplani, D; Daley, F; Haider, S; Shah, V; Sawyer, EJ; Howard, BA (2017-10)
      Here, we show that SOX11, an embryonic mammary marker that is normally silent in postnatal breast cells, is expressed in many oestrogen receptor-negative preinvasive ductal carcinoma in situ (DCIS) lesions. Mature mammary ...