Now showing items 21-29 of 29

    • Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. 

      Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; Khan, K; Lampis, A; Eason, K; Huntingford, I; Burke, R; Rata, M; Koh, D-M; Tunariu, N; Collins, D; Hulkki-Wilson, S; Ragulan, C; Spiteri, I; Moorcraft, SY; Chau, I; Rao, S; Watkins, D; Fotiadis, N; Bali, M; Darvish-Damavandi, M; Lote, H; Eltahir, Z; Smyth, EC; Begum, R; Clarke, PA; Hahne, JC; Dowsett, M; de Bono, J; Workman, P; Sadanandam, A; Fassan, M; Sansom, OJ; Eccles, S; Starling, N; Braconi, C; Sottoriva, A; Robinson, SP; Cunningham, D; Valeri, N (2018-02)
      Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ...
    • Pediatric and adult glioblastoma radiosensitization induced by PI3K/mTOR inhibition causes early metabolic alterations detected by nuclear magnetic resonance spectroscopy. 

      Agliano, A; Balarajah, G; Ciobota, DM; Sidhu, J; Clarke, PA; Jones, C; Workman, P; Leach, MO; Al-Saffar, NMS (2017-07)
      Poor outcome for patients with glioblastomas is often associated with radioresistance. PI3K/mTOR pathway deregulation has been correlated with radioresistance; therefore, PI3K/mTOR inhibition could render tumors radiosensitive. ...
    • A PI3K- and GTPase-independent Rac1-mTOR mechanism mediates MET-driven anchorage-independent cell growth but not migration. 

      Hervieu, A; Heuss, SF; Zhang, C; Barrow-McGee, R; Joffre, C; Ménard, L; Clarke, PA; Kermorgant, S (2020-06-23)
      Receptor tyrosine kinases (RTKs) are often overexpressed or mutated in cancers and drive tumor growth and metastasis. In the current model of RTK signaling, including that of MET, downstream phosphatidylinositol 3-kinase ...
    • Restricting direct interaction of CDC37 with HSP90 does not compromise chaperoning of client proteins. 

      Smith, JR; de Billy, E; Hobbs, S; Powers, M; Prodromou, C; Pearl, L; Clarke, PA; Workman, P (2015-01)
      The HSP90 molecular chaperone plays a key role in the maturation, stability and activation of its clients, including many oncogenic proteins. Kinases are a substantial and important subset of clients requiring the key ...
    • RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses. 

      Dolly, SO; Gurden, MD; Drosopoulos, K; Clarke, P; de Bono, J; Kaye, S; Workman, P; Linardopoulos, S (2017-09)
      <h4>Background</h4>F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently ...
    • A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease. 

      Dale, T; Clarke, PA; Esdar, C; Waalboer, D; Adeniji-Popoola, O; Ortiz-Ruiz, M-J; Mallinger, A; Samant, RS; Czodrowski, P; Musil, D; Schwarz, D; Schneider, K; Stubbs, M; Ewan, K; Fraser, E; TePoele, R; Court, W; Box, G; Valenti, M; de Haven Brandon, A; Gowan, S; Rohdich, F; Raynaud, F; Schneider, R; Poeschke, O; Blaukat, A; Workman, P; Schiemann, K; Eccles, SA; Wienke, D; Blagg, J (2015-12)
      There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT ...
    • Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases. 

      Zhang, C; Stockwell, SR; Elbanna, M; Ketteler, R; Freeman, J; Al-Lazikani, B; Eccles, S; De Haven Brandon, A; Raynaud, F; Hayes, A; Clarke, PA; Workman, P; Mittnacht, S (2019-07-12)
      Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on ...
    • Small-molecule targeting of brachyury transcription factor addiction in chordoma. 

      Sharifnia, T; Wawer, MJ; Chen, T; Huang, Q-Y; Weir, BA; Sizemore, A; Lawlor, MA; Goodale, A; Cowley, GS; Vazquez, F; Ott, CJ; Francis, JM; Sassi, S; Cogswell, P; Sheppard, HE; Zhang, T; Gray, NS; Clarke, PA; Blagg, J; Workman, P; Sommer, J; Hornicek, F; Root, DE; Hahn, WC; Bradner, JE; Wong, KK; Clemons, PA; Lin, CY; Kotz, JD; Schreiber, SL (2019-02)
      Chordoma is a primary bone cancer with no approved therapy<sup>1</sup>. The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic ...
    • Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening. 

      Czodrowski, P; Mallinger, A; Wienke, D; Esdar, C; Pöschke, O; Busch, M; Rohdich, F; Eccles, SA; Ortiz-Ruiz, M-J; Schneider, R; Raynaud, FI; Clarke, PA; Musil, D; Schwarz, D; Dale, T; Urbahns, K; Blagg, J; Schiemann, K (2016-10-07)
      The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ...