Now showing items 1-20 of 129

    • 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 ...
    • Acquiring evidence for precision prostate cancer care. 

      Mateo, J; Carreira, S; de Bono, JS (2017-05-01)
    • 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 (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 ...
    • 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 (2017-10-16)
      Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterised 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 (2017-10-05)
      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 ...
    • Characterisation of the Phosphatidylinositol 3-Kinase Pathway in Non-Small Cell Lung Cancer Cells Isolated from Pleural Effusions. 

      Puglisi, M; Stewart, A; Thavasu, P; Frow, M; Carreira, S; Minchom, A; Punwani, R; Bhosle, J; Popat, S; Ratoff, J; de Bono, J; Yap, TA; O''Brien, M; Banerji, U (2016-01)
      We hypothesised that it was possible to quantify phosphorylation of important nodes in the phosphatidylinositol 3-kinase (PI3K) pathway in cancer cells isolated from pleural effusions of patients with non-small cell lung ...
    • Characterization of Hedgehog Acyltransferase Inhibitors Identifies a Small Molecule Probe for Hedgehog Signaling by Cancer Cells. 

      Rodgers, UR; Lanyon-Hogg, T; Masumoto, N; Ritzefeld, M; Burke, R; Blagg, J; Magee, AI; Tate, EW
      The Sonic Hedgehog (Shh) signaling pathway plays a critical role during embryonic development and cancer progression. N-terminal palmitoylation of Shh by Hedgehog acyltransferase (Hhat) is essential for efficient signaling, ...
    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CK; Wai, P; Lambros, MB; Samartzis, EP; Dedes, KJ; Frankum, J; Bajrami, I; Kopec, A; Mackay, A; A'hern, R; Fenwick, K; Kozarewa, I; Hakas, J; Mitsopoulos, C; Hardisson, D; Lord, CJ; Kumar-Sinha, C; Ashworth, A; Weigelt, B; Sapino, A; Chinnaiyan, AM; Maher, CA; Reis-Filho, JS (2014-04)
      Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen ...
    • Characterizing and targeting PDGFRA alterations in pediatric high-grade glioma. 

      Koschmann, C; Zamler, D; MacKay, A; Robinson, D; Wu, YM; Doherty, R; Marini, B; Tran, D; Garton, H; Muraszko, K; Robertson, P; Leonard, M; Zhao, L; Bixby, D; Peterson, L; Camelo-Piragua, S; Jones, C; Mody, R; Lowenstein, PR; Castro, MG (2016-08-25)
      Pediatric high-grade glioma (HGG, WHO Grade III and IV) is a devastating brain tumor with a median survival of less than two years. PDGFRA is frequently mutated/ amplified in pediatric HGG, but the significance of this ...