Recent submissions

Now showing items 21-40 of 3420

    • How RhoGEFs drive triple negative breast cancer cell invasion through the activation of YAP and TAZ 

      Pascual Vargas, P (2020-03-31)
      Dynamical remodelling of the cytoskeleton is essential for triple negative breast cancer metastasis (TNBC). Cell shape is regulated by RhoGEFs which activate Rho GTPases resulting in changes in actin polymerisation, ...

    • Cancer cell killing by target antigen engagement with engineered complementary intracellular antibody single domains fused to pro-caspase3. 

      Chambers, JS; Brend, T; Rabbitts, TH (2019-06-12)
      Many tumour causing proteins, such as those expressed after chromosomal translocations or from point mutations, are intracellular and are not enzymes per se amenable to conventional drug targeting. We previously demonstrated ...

    • KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe. 

      Bery, N; Legg, S; Debreczeni, J; Breed, J; Embrey, K; Stubbs, C; Kolasinska-Zwierz, P; Barrett, N; Marwood, R; Watson, J; Tart, J; Overman, R; Miller, A; Phillips, C; Minter, R; Rabbitts, TH (2019-06-13)
      Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ...

    • Diverse AR Gene Rearrangements Mediate Resistance to Androgen Receptor Inhibitors in Metastatic Prostate Cancer. 

      Li, Y; Yang, R; Henzler, CM; Ho, Y; Passow, C; Auch, B; Carreira, S; Nava Rodrigues, D; Bertan, C; Hwang, TH; Quigley, DA; Dang, HX; Morrissey, C; Fraser, M; Plymate, SR; Maher, CA; Feng, FY; de Bono, JS; Dehm, SM (2020-01-13)
      PURPOSE:Prostate cancer is the second leading cause of male cancer deaths. Castration-resistant prostate cancer (CRPC) is a lethal stage of the disease that emerges when endocrine therapies are no longer effective at ...

    • Circulating cell-free DNA: Translating prostate cancer genomics into clinical care. 

      Gasi Tandefelt, D; de Bono, J (2020-01-16)
      Only in the past decade tremendous advances have been made in understanding prostate cancer genomics and consequently in applying new treatment strategies. As options regarding treatments are increasing so are the challenges ...

    • CALIBER - A phase II randomised feasibility trial of chemoablation with mitomycin versus surgical management in low risk non-muscle invasive bladder cancer. 

      Mostafid, AH; Porta, N; Cresswell, J; Griffiths, T; Kelly, JD; Penegar, SR; Davenport, K; McGrath, JS; Campain, N; Cooke, P; Masood, S; Knowles, MA; Feber, A; Knight, A; Catto, JW; Lewis, R; Hall, E (2020-03-03)
      OBJECTIVES:To evaluate the activity of intravesical mitomycin C (MMC) to ablate recurrent low risk non-muscle invasive bladder cancer (NMIBC) and assess whether it may enable patients to avoid surgical intervention for ...

    • Capivasertib Plus Paclitaxel Versus Placebo Plus Paclitaxel As First-Line Therapy for Metastatic Triple-Negative Breast Cancer: The PAKT Trial. 

      Schmid, P; Abraham, J; Chan, S; Wheatley, D; Brunt, AM; Nemsadze, G; Baird, RD; Park, YH; Hall, PS; Perren, T; Stein, RC; Mangel, L; Ferrero, J-M; Phillips, M; Conibear, J; Cortes, J; Foxley, A; de Bruin, EC; McEwen, R; Stetson, D; Dougherty, B; Sarker, S-J; Prendergast, A; McLaughlin-Callan, M; Burgess, M; Lawrence, C; Cartwright, H; Mousa, K; Turner, NC (2020-02)
      PURPOSE:The phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is frequently activated in triple-negative breast cancer (TNBC). The AKT inhibitor capivasertib has shown preclinical activity in TNBC models, and drug ...

    • Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women. 

      Schoemaker, MJ; Nichols, HB; Wright, LB; Brook, MN; Jones, ME; O'Brien, KM; Adami, H-O; Baglietto, L; Bernstein, L; Bertrand, KA; Boutron-Ruault, M-C; Chen, Y; Connor, AE; Dossus, L; Eliassen, AH; Giles, GG; Gram, IT; Hankinson, SE; Kaaks, R; Key, TJ; Kirsh, VA; Kitahara, CM; Larsson, SC; Linet, M; Ma, H; Milne, RL; Ozasa, K; Palmer, JR; Riboli, E; Rohan, TE; Sacerdote, C; Sadakane, A; Sund, M; Tamimi, RM; Trichopoulou, A; Ursin, G; Visvanathan, K; Weiderpass, E; Willett, WC; Wolk, A; Zeleniuch-Jacquotte, A; Sandler, DP; Swerdlow, AJ (2020-02-03)
      Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies ...

    • IGF1-mediated human embryonic stem cell self-renewal recapitulates the embryonic niche. 

      Wamaitha, SE; Grybel, KJ; Alanis-Lobato, G; Gerri, C; Ogushi, S; McCarthy, A; Mahadevaiah, SK; Healy, L; Lea, RA; Molina-Arcas, M; Devito, LG; Elder, K; Snell, P; Christie, L; Downward, J; Turner, JMA; Niakan, KK (2020-02-07)
      Our understanding of the signalling pathways regulating early human development is limited, despite their fundamental biological importance. Here, we mine transcriptomics datasets to investigate signalling in the human ...

    • Long-term outcomes with intensive induction chemotherapy (carboplatin, bleomycin, vincristine and cisplatin/bleomycin, etoposide and cisplatin) and standard bleomycin, etoposide and cisplatin in poor prognosis germ cell tumours: A randomised phase II trial (ISRCTN53643604). 

      Cafferty, FH; White, JD; Shamash, J; Hennig, I; Stenning, SP; Huddart, RA; TE23 Trial Management Group and Collaborators (2020-03)
      BACKGROUND:Up to 50% of men with poor prognosis, non-seminoma germ cell tumours (GCTs) die with standard BEP (bleomycin, etoposide and cisplatin) chemotherapy. An intensive regimen, CBOP/BEP (carboplatin, bleomycin, ...

    • The kinase polypharmacology landscape of clinical PARP inhibitors. 

      Antolin, AA; Ameratunga, M; Banerji, U; Clarke, PA; Workman, P; Al-Lazikani, B (2020-02-17)
      Polypharmacology plays an important role in defining response and adverse effects of drugs. For some mechanisms, experimentally mapping polypharmacology is commonplace, although this is typically done within the same protein ...

    • Polygenic risk-tailored screening for prostate cancer: A benefit-harm and cost-effectiveness modelling study. 

      Callender, T; Emberton, M; Morris, S; Eeles, R; Eeles, R; Kote-Jarai, Z; Pharoah, PDP; Pashayan, N (2019-12-20)
      BACKGROUND:The United States Preventive Services Task Force supports individualised decision-making for prostate-specific antigen (PSA)-based screening in men aged 55-69. Knowing how the potential benefits and harms of ...

    • Fine-mapping of 150 breast cancer risk regions identifies 191 likely target genes. 

      Fachal, L; Aschard, H; Beesley, J; Barnes, DR; Allen, J; Kar, S; Pooley, KA; Dennis, J; Michailidou, K; Turman, C; Soucy, P; Lemaçon, A; Lush, M; Tyrer, JP; Ghoussaini, M; Moradi Marjaneh, M; Jiang, X; Agata, S; Aittomäki, K; Alonso, MR; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Arason, A; Arndt, V; Aronson, KJ; Arun, BK; Auber, B; Auer, PL; Azzollini, J; Balmaña, J; Barkardottir, RB; Barrowdale, D; Beeghly-Fadiel, A; Benitez, J; Bermisheva, M; Białkowska, K; Blanco, AM; Blomqvist, C; Blot, W; Bogdanova, NV; Bojesen, SE; Bolla, MK; Bonanni, B; Borg, A; Bosse, K; Brauch, H; Brenner, H; Briceno, I; Brock, IW; Brooks-Wilson, A; Brüning, T; Burwinkel, B; Buys, SS; Cai, Q; Caldés, T; Caligo, MA; Camp, NJ; Campbell, I; Canzian, F; Carroll, JS; Carter, BD; Castelao, JE; Chiquette, J; Christiansen, H; Chung, WK; Claes, KBM; Clarke, CL; GEMO Study Collaborators; EMBRACE Collaborators; Collée, JM; Cornelissen, S; Couch, FJ; Cox, A; Cross, SS; Cybulski, C; Czene, K; Daly, MB; de la Hoya, M; Devilee, P; Diez, O; Ding, YC; Dite, GS; Domchek, SM; Dörk, T; Dos-Santos-Silva, I; Droit, A; Dubois, S; Dumont, M; Duran, M; Durcan, L; Dwek, M; Eccles, DM; Engel, C; Eriksson, M; Evans, DG; Fasching, PA; Fletcher, O; Floris, G; Flyger, H; Foretova, L; Foulkes, WD; Friedman, E; Fritschi, L; Frost, D; Gabrielson, M; Gago-Dominguez, M; Gambino, G; Ganz, PA; Gapstur, SM; Garber, J; García-Sáenz, JA; Gaudet, MM; Georgoulias, V; Giles, GG; Glendon, G; Godwin, AK; Goldberg, MS; Goldgar, DE; González-Neira, A; Tibiletti, MG; Greene, MH; Grip, M; Gronwald, J; Grundy, A; Guénel, P; Hahnen, E; Haiman, CA; Håkansson, N; Hall, P; Hamann, U; Harrington, PA; Hartikainen, JM; Hartman, M; He, W; Healey, CS; Heemskerk-Gerritsen, BAM; Heyworth, J; Hillemanns, P; Hogervorst, FBL; Hollestelle, A; Hooning, MJ; Hopper, JL; Howell, A; Huang, G; Hulick, PJ; Imyanitov, EN; KConFab Investigators; HEBON Investigators; ABCTB Investigators; Isaacs, C; Iwasaki, M; Jager, A; Jakimovska, M; Jakubowska, A; James, PA; Janavicius, R; Jankowitz, RC; John, EM; Johnson, N; Jones, ME; Jukkola-Vuorinen, A; Jung, A; Kaaks, R; Kang, D; Kapoor, PM; Karlan, BY; Keeman, R; Kerin, MJ; Khusnutdinova, E; Kiiski, JI; Kirk, J; Kitahara, CM; Ko, Y-D; Konstantopoulou, I; Kosma, V-M; Koutros, S; Kubelka-Sabit, K; Kwong, A; Kyriacou, K; Laitman, Y; Lambrechts, D; Lee, E; Leslie, G; Lester, J; Lesueur, F; Lindblom, A; Lo, W-Y; Long, J; Lophatananon, A; Loud, JT; Lubiński, J; MacInnis, RJ; Maishman, T; Makalic, E; Mannermaa, A; Manoochehri, M; Manoukian, S; Margolin, S; Martinez, ME; Matsuo, K; Maurer, T; Mavroudis, D; Mayes, R; McGuffog, L; McLean, C; Mebirouk, N; Meindl, A; Miller, A; Miller, N; Montagna, M; Moreno, F; Muir, K; Mulligan, AM; Muñoz-Garzon, VM; Muranen, TA; Narod, SA; Nassir, R; Nathanson, KL; Neuhausen, SL; Nevanlinna, H; Neven, P; Nielsen, FC; Nikitina-Zake, L; Norman, A; Offit, K; Olah, E; Olopade, OI; Olsson, H; Orr, N; Osorio, A; Pankratz, VS; Papp, J; Park, SK; Park-Simon, T-W; Parsons, MT; Paul, J; Pedersen, IS; Peissel, B; Peshkin, B; Peterlongo, P; Peto, J; Plaseska-Karanfilska, D; Prajzendanc, K; Prentice, R; Presneau, N; Prokofyeva, D; Pujana, MA; Pylkäs, K; Radice, P; Ramus, SJ; Rantala, J; Rau-Murthy, R; Rennert, G; Risch, HA; Robson, M; Romero, A; Rossing, M; Saloustros, E; Sánchez-Herrero, E; Sandler, DP; Santamariña, M; Saunders, C; Sawyer, EJ; Scheuner, MT; Schmidt, DF; Schmutzler, RK; Schneeweiss, A; Schoemaker, MJ; Schöttker, B; Schürmann, P; Scott, C; Scott, RJ; Senter, L; Seynaeve, CM; Shah, M; Sharma, P; Shen, C-Y; Shu, X-O; Singer, CF; Slavin, TP; Smichkoska, S; Southey, MC; Spinelli, JJ; Spurdle, AB; Stone, J; Stoppa-Lyonnet, D; Sutter, C; Swerdlow, AJ; Tamimi, RM; Tan, YY; Tapper, WJ; Taylor, JA; Teixeira, MR; Tengström, M; Teo, SH; Terry, MB; Teulé, A; Thomassen, M; Thull, DL; Tischkowitz, M; Toland, AE; Tollenaar, RAEM; Tomlinson, I; Torres, D; Torres-Mejía, G; Troester, MA; Truong, T; Tung, N; Tzardi, M; Ulmer, H-U; Vachon, CM; van Asperen, CJ; van der Kolk, LE; van Rensburg, EJ; Vega, A; Viel, A; Vijai, J; Vogel, MJ; Wang, Q; Wappenschmidt, B; Weinberg, CR; Weitzel, JN; Wendt, C; Wildiers, H; Winqvist, R; Wolk, A; Wu, AH; Yannoukakos, D; Zhang, Y; Zheng, W; Hunter, D; Pharoah, PDP; Chang-Claude, J; García-Closas, M; Schmidt, MK; Milne, RL; Kristensen, VN; French, JD; Edwards, SL; Antoniou, AC; Chenevix-Trench, G; Simard, J; Easton, DF; Kraft, P; Dunning, AM (2020-01-07)
      Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association ...

    • Phenome-wide association analysis of LDL-cholesterol lowering genetic variants in PCSK9. 

      Schmidt, AF; Holmes, MV; Preiss, D; Swerdlow, DI; Denaxas, S; Fatemifar, G; Faraway, R; Finan, C; Valentine, D; Fairhurst-Hunter, Z; Hartwig, FP; Horta, BL; Hypponen, E; Power, C; Moldovan, M; van Iperen, E; Hovingh, K; Demuth, I; Norman, K; Steinhagen-Thiessen, E; Demuth, J; Bertram, L; Lill, CM; Coassin, S; Willeit, J; Kiechl, S; Willeit, K; Mason, D; Wright, J; Morris, R; Wanamethee, G; Whincup, P; Ben-Shlomo, Y; McLachlan, S; Price, JF; Kivimaki, M; Welch, C; Sanchez-Galvez, A; Marques-Vidal, P; Nicolaides, A; Panayiotou, AG; Onland-Moret, NC; van der Schouw, YT; Matullo, G; Fiorito, G; Guarrera, S; Sacerdote, C; Wareham, NJ; Langenberg, C; Scott, RA; Luan, J; Bobak, M; Malyutina, S; Pająk, A; Kubinova, R; Tamosiunas, A; Pikhart, H; Grarup, N; Pedersen, O; Hansen, T; Linneberg, A; Jess, T; Cooper, J; Humphries, SE; Brilliant, M; Kitchner, T; Hakonarson, H; Carrell, DS; McCarty, CA; Lester, KH; Larson, EB; Crosslin, DR; de Andrade, M; Roden, DM; Denny, JC; Carty, C; Hancock, S; Attia, J; Holliday, E; Scott, R; Schofield, P; O'Donnell, M; Yusuf, S; Chong, M; Pare, G; van der Harst, P; Said, MA; Eppinga, RN; Verweij, N; Snieder, H; Lifelines Cohort authors; Christen, T; Mook-Kanamori, DO; ICBP Consortium; Gustafsson, S; Lind, L; Ingelsson, E; Pazoki, R; Franco, O; Hofman, A; Uitterlinden, A; Dehghan, A; Teumer, A; Baumeister, S; Dörr, M; Lerch, MM; Völker, U; Völzke, H; Ward, J; Pell, JP; Meade, T; Christophersen, IE; Maitland-van der Zee, AH; Baranova, EV; Young, R; Ford, I; Campbell, A; Padmanabhan, S; Bots, ML; Grobbee, DE; Froguel, P; Thuillier, D; Roussel, R; Bonnefond, A; Cariou, B; Smart, M; Bao, Y; Kumari, M; Mahajan, A; Hopewell, JC; Seshadri, S; METASTROKE Consortium of the ISGC; Dale, C; Costa, RPE; Ridker, PM; Chasman, DI; Reiner, AP; Ritchie, MD; Lange, LA; Cornish, AJ; Dobbins, SE; Hemminki, K; Kinnersley, B; Sanson, M; Labreche, K; Simon, M; Bondy, M; Law, P; Speedy, H; Allan, J; Li, N; Went, M; Weinhold, N; Morgan, G; Sonneveld, P; Nilsson, B; Goldschmidt, H; Sud, A; Engert, A; Hansson, M; Hemingway, H; Asselbergs, FW; Patel, RS; Keating, BJ; Sattar, N; Houlston, R; Casas, JP; Hingorani, AD (2019-10-29)
      BACKGROUND:We characterised the phenotypic consequence of genetic variation at the PCSK9 locus and compared findings with recent trials of pharmacological inhibitors of PCSK9. METHODS:Published and individual participant ...

    • 3D tumour spheroids for the prediction of the effects of radiation and hyperthermia treatments. 

      Brüningk, SC; Rivens, I; Box, C; Oelfke, U; Ter Haar, G (2020-02-03)
      For multimodality therapies such as the combination of hyperthermia and radiation, quantification of biological effects is key for dose prescription and response prediction. Tumour spheroids have a microenvironment that ...

    • Measuring single cell divisions in human tissues from multi-region sequencing data. 

      Werner, B; Case, J; Williams, MJ; Chkhaidze, K; Temko, D; Fernández-Mateos, J; Cresswell, GD; Nichol, D; Cross, W; Spiteri, I; Huang, W; Tomlinson, IPM; Barnes, CP; Graham, TA; Sottoriva, A (2020-02-25)
      Both normal tissue development and cancer growth are driven by a branching process of cell division and mutation accumulation that leads to intra-tissue genetic heterogeneity. However, quantifying somatic evolution in ...

    • Lenalidomide, dexamethasone and alemtuzumab or ofatumumab in high-risk chronic lymphocytic leukaemia: final results of the NCRI CLL210 trial. 

      Pettitt, AR; Jackson, R; Cicconi, S; Polydoros, F; Yap, C; Dodd, J; Bickerstaff, M; Stackpoole, M; Khan, UT; Carruthers, S; Oates, M; Lin, K; Coupland, SE; Menon, G; Kalakonda, N; McCarthy, H; Bloor, A; Schuh, A; Duncombe, A; Dearden, C; Fegan, C; Kennedy, B; Walewska, R; Marshall, S; Fox, CP; Hillmen, P (2020-02-13)

    • Prediction of Benefit from Checkpoint Inhibitors in Mismatch Repair Deficient Metastatic Colorectal Cancer: Role of Tumor Infiltrating Lymphocytes. 

      Loupakis, F; Depetris, I; Biason, P; Intini, R; Prete, AA; Leone, F; Lombardi, P; Filippi, R; Spallanzani, A; Cascinu, S; Bonetti, LR; Maddalena, G; Valeri, N; Sottoriva, A; Zapata, L; Salmaso, R; Munari, G; Rugge, M; Dei Tos, AP; Golovato, J; Sanborn, JZ; Nguyen, A; Schirripa, M; Zagonel, V; Lonardi, S; Fassan, M (2020-01-22)
      BACKGROUND:Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC); however, specific predictive biomarkers are lacking. ...

    • Immune and muli-omic profiling for molecular classification and biomarker discovery in soft tissue sarcoma 

      Lee, A (2020-02-29)
      Soft tissue sarcomas (STS) are a group of over 50 rare cancers of mesenchymal origin. Classification of STS is primarily based on histological characteristics of tumours. Novel biomarkers are required that account for the ...

    • Bromodomain inhibitor OTX015 in patients with acute leukaemia: a dose-escalation, phase 1 study. 

      Berthon, C; Raffoux, E; Thomas, X; Vey, N; Gomez-Roca, C; Yee, K; Taussig, DC; Rezai, K; Roumier, C; Herait, P; Kahatt, C; Quesnel, B; Michallet, M; Recher, C; Lokiec, F; Preudhomme, C; Dombret, H (2016-04)
      Bromodomain and extraterminal (BET) proteins are chromatin readers that preferentially affect the transcription of genes with super-enhancers, including oncogenes. BET proteins bind acetylated histone tails via their ...