Now showing items 1-20 of 180

    • 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
      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
    • 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 ...
    • 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 ...
    • 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 ...
    • Applications of Systematic Molecular Scaffold Enumeration to Enrich Structure-Activity Relationship Information. 

      Mok, NY; Brown, N
      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 ...
    • 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
      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 ...
    • Aurora B prevents premature removal of spindle assembly checkpoint proteins from the kinetochore: A key role for Aurora B in mitosis. 

      Gurden, MD; Anderhub, SJ; Faisal, A; Linardopoulos, S (2016-07-18)
      Accurate chromosome segregation is dependent on the spindle assembly checkpoint (SAC). In current models, the key direct role of Aurora B in the SAC has been suggested to be to promote rapid kinetochore localisation of ...
    • Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer. 

      Lote, H; Spiteri, I; Ermini, L; Vatsiou, A; Roy, A; McDonald, A; Maka, N; Balsitis, M; Bose, N; Simbolo, M; Mafficini, A; Lampis, A; Hahne, JC; Trevisani, F; Eltahir, Z; Mentrasti, G; Findlay, C; Kalkman, EAJ; Punta, M; Werner, B; Lise, S; Aktipis, A; Maley, C; Greaves, M; Braconi, C; White, J; Fassan, M; Scarpa, A; Sottoriva, A; Valeri, N
      Background: Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but ...
    • Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses. 

      Lorente, D; Omlin, A; Zafeiriou, Z; Nava-Rodrigues, D; Pérez-López, R; Pezaro, C; Mehra, N; Sheridan, E; Figueiredo, I; Riisnaes, R; Miranda, S; Crespo, M; Flohr, P; Mateo, J; Altavilla, A; Ferraldeschi, R; Bianchini, D; Attard, G; Tunariu, N; de Bono, J (2016-05-05)
      The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of ...
    • CDK4/6 Inhibitors: Promising Opportunities beyond Breast Cancer. 

      Lim, JS; Turner, NC; Yap, TA (2016-07)
      Patnaik and colleagues report on the safety, pharmacokinetics, pharmacodynamics, and preliminary efficacy of abemaciclib for the treatment of advanced solid cancers, demonstrating antitumor activity in advanced breast ...
    • Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy. 

      Faisal, A; Mak, GWY; Gurden, MD; Xavier, CPR; Anderhub, SJ; Innocenti, P; Westwood, IM; Naud, S; Hayes, A; Box, G; Valenti, MR; De Haven Brandon, AK; O'Fee, L; Schmitt, J; Woodward, HL; Burke, R; vanMontfort, RLM; Blagg, J; Raynaud, FI; Eccles, SA; Hoelder, S; Linardopoulos, S (2017-04-25)
      BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ...
    • Characterisation of the immune-related transcriptome in resected biliary tract cancers. 

      Ghidini, M; Cascione, L; Carotenuto, P; Lampis, A; Trevisani, F; Previdi, MC; Hahne, JC; Said-Huntingford, I; Raj, M; Zerbi, A; Mescoli, C; Cillo, U; Rugge, M; Roncalli, M; Torzilli, G; Rimassa, L; Santoro, A; Valeri, N; Fassan, M; Braconi, C
      Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling ...