Now showing items 1-20 of 328

    • 2,8-Disubstituted-1,6-Naphthyridines and 4,6-Disubstituted-Isoquinolines with Potent, Selective Affinity for CDK8/19. 

      Mallinger, A; Schiemann, K; Rink, C; Sejberg, J; Honey, MA; Czodrowski, P; Stubbs, M; Poeschke, O; Busch, M; Schneider, R; Schwarz, D; Musil, D; Burke, R; Urbahns, K; Workman, P; Wienke, D; Clarke, PA; Raynaud, FI; Eccles, SA; Esdar, C; Rohdich, F; Blagg, J (2016-06)
      We demonstrate a designed scaffold-hop approach to the discovery of 2,8-disubstituted-1,6-naphthyridine- and 4,6-disubstituted-isoquinoline-based dual CDK8/19 ligands. Optimized compounds in both series exhibited rapid ...
    • Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project. 

      Moreno, L; Caron, H; Geoerger, B; Eggert, A; Schleiermacher, G; Brock, P; Valteau-Couanet, D; Chesler, L; Schulte, JH; De Preter, K; Molenaar, J; Schramm, A; Eilers, M; Van Maerken, T; Johnsen, JI; Garrett, M; George, SL; Tweddle, DA; Kogner, P; Berthold, F; Koster, J; Barone, G; Tucker, ER; Marshall, L; Herold, R; Sterba, J; Norga, K; Vassal, G; Pearson, AD (2017-08)
      INTRODUCTION: Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term ...
    • Acquiring evidence for precision prostate cancer care. 

      Mateo, J; Carreira, S; de Bono, JS (2017-05-01)
    • Activation of the Farnesoid X-receptor in breast cancer cell lines results in cytotoxicity but not increased migration potential 

      Swales, Karen (2016)
      Breast cancer is the commonest form of cancer in women, but successful treatment is confounded by the heterogeneous nature of breast tumours: Effective treatments exist for hormone-sensitive tumours, but triple-negative ...
    • Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial. 

      Bisogno, G; Jenney, M; Bergeron, C; Gallego Melcón, S; Ferrari, A; Oberlin, O; Carli, M; Stevens, M; Kelsey, A; De Paoli, A; Gaze, MN; Martelli, H; Devalck, C; Merks, JH; Ben-Arush, M; Glosli, H; Chisholm, J; Orbach, D; Minard-Colin, V; De Salvo, GL; European paediatric Soft tissue sarcoma Study Group (2018-08)
      BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug ...
    • Adjuvant chemotherapy for resected biliary tract cancers: a systematic review and meta-analysis. 

      Ghidini, M; Tomasello, G; Botticelli, A; Barni, S; Zabbialini, G; Seghezzi, S; Passalacqua, R; Braconi, C; Petrelli, F (2017-09)
      INTRODUCTION: The use of adjuvant treatment (AT) in resected biliary tract cancers (BTC) is still controversial. No efficacy comparison has been performed between chemotherapy (CT) and chemoradiotherapy (CTRT). A systematic ...
    • Advances in the Development of Molecularly Targeted Agents in Non-Small-Cell Lung Cancer. 

      Dolly, SO; Collins, DC; Sundar, R; Popat, S; Yap, TA (2017-05)
      Non-small-cell lung cancer (NSCLC) remains a significant global health challenge and the leading cause of cancer-related mortality. The traditional 'one-size-fits-all' treatment approach has now evolved into one that ...
    • Affibody-based PET imaging to guide EGFR-targeted cancer therapy in head and neck squamous cell cancer models. 

      Burley, TA; Pieve, CD; Martins, CD; Ciobota, DM; Allott, L; Oyen, WJG; Harrington, KJ; Smith, G; Kramer-Marek, G (2018-09-13)
      In head and neck squamous cell carcinoma (HNSCC), the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR mAb ...
    • AKT Inhibition in Solid Tumors With AKT1 Mutations. 

      Hyman, DM; Smyth, LM; Donoghue, MTA; Westin, SN; Bedard, PL; Dean, EJ; Bando, H; El-Khoueiry, AB; Pérez-Fidalgo, JA; Mita, A; Schellens, JHM; Chang, MT; Reichel, JB; Bouvier, N; Selcuklu, SD; Soumerai, TE; Torrisi, J; Erinjeri, JP; Ambrose, H; Barrett, JC; Dougherty, B; Foxley, A; Lindemann, JPO; McEwen, R; Pass, M; Schiavon, G; Berger, MF; Chandarlapaty, S; Solit, DB; Banerji, U; Baselga, J; Taylor, BS (2017-07-10)
      Purpose AKT1 E17K mutations are oncogenic and occur in many cancers at a low prevalence. We performed a multihistology basket study of AZD5363, an ATP-competitive pan-AKT kinase inhibitor, to determine the preliminary ...
    • Algorithms for chemoinformatics 

      Brown, N (WILEY PERIODICALS, INC, 2011-09)
      The field of chemoinformatics makes use of a great number of different computational algorithms from mathematics and computer science as well as algorithms that are defined explicitly for challenges specific to chemoinformatics. ...
    • The ALK inhibitor PF-06463922 is effective as a single agent in neuroblastoma driven by expression of ALK and MYCN. 

      Guan, J; Tucker, ER; Wan, H; Chand, D; Danielson, LS; Ruuth, K; El Wakil, A; Witek, B; Jamin, Y; Umapathy, G; Robinson, SP; Johnson, TW; Smeal, T; Martinsson, T; Chesler, L; Palmer, RH; Hallberg, B (2016-09)
      The first-in-class inhibitor of ALK, c-MET and ROS1, crizotinib (Xalkori), has shown remarkable clinical efficacy in treatment of ALK-positive non-small cell lung cancer. However, in neuroblastoma, activating mutations in ...
    • AMPK-independent inhibition of human macrophage ER stress response by AICAR. 

      Boß, M; Newbatt, Y; Gupta, S; Collins, I; Brüne, B; Namgaladze, D (2016-01)
      Obesity-associated insulin resistance is driven by inflammatory processes in response to metabolic overload. Obesity-associated inflammation can be recapitulated in cell culture by exposing macrophages to saturated fatty ...
    • Antibody-drug conjugates--an emerging class of cancer treatment. 

      Diamantis, N; Banerji, U (2016-02)
      Antibody-drug conjugates (ADCs) are an emerging novel class of anticancer treatment agents that combines the selectivity of targeted treatment with the cytotoxic potency of chemotherapy drugs. New linker technology associated ...
    • APC/C is an essential regulator of centrosome clustering. 

      Drosopoulos, K; Tang, C; Chao, WC; Linardopoulos, S (2014-01)
      Centrosome amplification has been extensively associated with cancer. Cancer cells with extra centrosomes have the ability to cluster the extra centrosomes and divide in a bipolar fashion. Although a number of proteins ...
    • Applications of Systematic Molecular Scaffold Enumeration to Enrich Structure-Activity Relationship Information. 

      Mok, NY; Brown, N (2017-01-23)
      Establishing structure-activity relationships (SARs) in hit identification during early stage drug discovery is important in accelerating hit confirmation and expansion. We describe the development of EnCore, a systematic ...
    • Assessing histone demethylase inhibitors in cells: lessons learned. 

      Hatch, SB; Yapp, C; Montenegro, RC; Savitsky, P; Gamble, V; Tumber, A; Ruda, GF; Bavetsias, V; Fedorov, O; Atrash, B; Raynaud, F; Lanigan, R; Carmichael, L; Tomlin, K; Burke, R; Westaway, SM; Brown, JA; Prinjha, RK; Martinez, ED; Oppermann, U; Schofield, CJ; Bountra, C; Kawamura, A; Blagg, J; Brennan, PE; Rossanese, O; Müller, S (2017)
      BACKGROUND: Histone lysine demethylases (KDMs) are of interest as drug targets due to their regulatory roles in chromatin organization and their tight associations with diseases including cancer and mental disorders. The ...
    • Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases. 

      Clarke, PA; Ortiz-Ruiz, M-J; TePoele, R; Adeniji-Popoola, O; Box, G; Court, W; Czasch, S; El Bawab, S; Esdar, C; Ewan, K; Gowan, S; De Haven Brandon, A; Hewitt, P; Hobbs, SM; Kaufmann, W; Mallinger, A; Raynaud, F; Roe, T; Rohdich, F; Schiemann, K; Simon, S; Schneider, R; Valenti, M; Weigt, S; Blagg, J; Blaukat, A; Dale, TC; Eccles, SA; Hecht, S; Urbahns, K; Workman, P; Wienke, D (2016-12-09)
      Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility ...
    • Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. 

      Büchel, G; Carstensen, A; Mak, K-Y; Roeschert, I; Leen, E; Sumara, O; Hofstetter, J; Herold, S; Kalb, J; Baluapuri, A; Poon, E; Kwok, C; Chesler, L; Maric, HM; Rickman, DS; Wolf, E; Bayliss, R; Walz, S; Eilers, M (2017-12-19)
      MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes ...
    • 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 (2017-12-15)
      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 ...