Now showing items 21-40 of 52

    • Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. 

      Aarts, M; Sharpe, R; Garcia-Murillas, I; Gevensleben, H; Hurd, MS; Shumway, SD; Toniatti, C; Ashworth, A; Turner, NC (2012-06)
      Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. ...
    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...
    • High-Level Clonal FGFR Amplification and Response to FGFR Inhibition in a Translational Clinical Trial. 

      Pearson, A; Smyth, E; Babina, IS; Herrera-Abreu, MT; Tarazona, N; Peckitt, C; Kilgour, E; Smith, NR; Geh, C; Rooney, C; Cutts, R; Campbell, J; Ning, J; Fenwick, K; Swain, A; Brown, G; Chua, S; Thomas, A; Johnston, SRD; Ajaz, M; Sumpter, K; Gillbanks, A; Watkins, D; Chau, I; Popat, S; Cunningham, D; Turner, NC (2016-08)
      FGFR1 and FGFR2 are amplified in many tumor types, yet what determines response to FGFR inhibition in amplified cancers is unknown. In a translational clinical trial, we show that gastric cancers with high-level clonal ...
    • HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target. 

      Fok, JHL; Hedayat, S; Zhang, L; Aronson, LI; Mirabella, F; Pawlyn, C; Bright, MD; Wardell, CP; Keats, JJ; De Billy, E; Rye, CS; Chessum, NEA; Jones, K; Morgan, GJ; Eccles, SA; Workman, P; Davies, FE (2018-05)
      Purpose: Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) ...
    • Mapping genetic vulnerabilities reveals BTK as a novel therapeutic target in oesophageal cancer. 

      Chong, IY; Aronson, L; Bryant, H; Gulati, A; Campbell, J; Elliott, R; Pettitt, S; Wilkerson, P; Lambros, MB; Reis-Filho, JS; Ramessur, A; Davidson, M; Chau, I; Cunningham, D; Ashworth, A; Lord, CJ (2018-10)
      OBJECTIVE:Oesophageal cancer is the seventh most common cause of cancer-related death worldwide. Disease relapse is frequent and treatment options are limited. DESIGN:To identify new biomarker-defined therapeutic approaches ...
    • MCT1 Inhibitor AZD3965 Increases Mitochondrial Metabolism, Facilitating Combination Therapy and Noninvasive Magnetic Resonance Spectroscopy. 

      Beloueche-Babari, M; Wantuch, S; Casals Galobart, T; Koniordou, M; Parkes, HG; Arunan, V; Chung, Y-L; Eykyn, TR; Smith, PD; Leach, MO (2017-11)
      Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination ...
    • Metabolic adaptability in metastatic breast cancer by AKR1B10-dependent balancing of glycolysis and fatty acid oxidation. 

      van Weverwijk, A; Koundouros, N; Iravani, M; Ashenden, M; Gao, Q; Poulogiannis, G; Jungwirth, U; Isacke, CM (2019-06-20)
      The different stages of the metastatic cascade present distinct metabolic challenges to tumour cells and an altered tumour metabolism associated with successful metastatic colonisation provides a therapeutic vulnerability ...
    • MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma. 

      Lampis, A; Carotenuto, P; Vlachogiannis, G; Cascione, L; Hedayat, S; Burke, R; Clarke, P; Bosma, E; Simbolo, M; Scarpa, A; Yu, S; Cole, R; Smyth, E; Mateos, JF; Begum, R; Hezelova, B; Eltahir, Z; Wotherspoon, A; Fotiadis, N; Bali, MA; Nepal, C; Khan, K; Stubbs, M; Hahne, JC; Gasparini, P; Guzzardo, V; Croce, CM; Eccles, S; Fassan, M; Cunningham, D; Andersen, JB; Workman, P; Valeri, N; Braconi, C (2018-03)
      BACKGROUND & AIMS:Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ...
    • Modeling Therapy Resistance in BRCA1/2-Mutant Cancers. 

      Dréan, A; Williamson, CT; Brough, R; Brandsma, I; Menon, M; Konde, A; Garcia-Murillas, I; Pemberton, HN; Frankum, J; Rafiq, R; Badham, N; Campbell, J; Gulati, A; Turner, NC; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-09)
      Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ...
    • Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma. 

      Ang, JE; Pal, A; Asad, YJ; Henley, AT; Valenti, M; Box, G; de Haven Brandon, A; Revell, VL; Skene, DJ; Venturi, M; Rueger, R; Meresse, V; Eccles, SA; de Bono, JS; Kaye, SB; Workman, P; Banerji, U; Raynaud, FI (2017-10)
      MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based ...
    • Monitoring the Vascular Response and Resistance to Sunitinib in Renal Cell Carcinoma In Vivo with Susceptibility Contrast MRI. 

      Robinson, SP; Boult, JKR; Vasudev, NS; Reynolds, AR (2017-08)
      Antiangiogenic therapy is efficacious in metastatic renal cell carcinoma (mRCC). However, the ability of antiangiogenic drugs to delay tumor progression and extend survival is limited, due to either innate or acquired drug ...
    • Near-infrared photoimmunotherapy targeting EGFR-Shedding new light on glioblastoma treatment. 

      Burley, TA; Mączyńska, J; Shah, A; Szopa, W; Harrington, KJ; Boult, JKR; Mrozek-Wilczkiewicz, A; Vinci, M; Bamber, JC; Kaspera, W; Kramer-Marek, G (2018-06)
      Glioblastomas (GBMs) are high-grade brain tumors, differentially driven by alterations (amplification, deletion or missense mutations) in the epidermal growth factor receptor (EGFR), that carry a poor prognosis of just ...
    • Noninvasive detection of carboxypeptidase G2 activity in vivo. 

      Jamin, Y; Smyth, L; Robinson, SP; Poon, ESC; Eykyn, TR; Springer, CJ; Leach, MO; Payne, GS (2011-05)
      The pseudomonad protein, carboxypeptidase G2 (CPG2), is a prodrug-activating enzyme utilized in the targeted chemotherapy strategies of antibody- and gene-directed enzyme prodrug therapy (ADEPT and GDEPT). We have developed ...
    • Noninvasive Imaging of Cycling Hypoxia in Head and Neck Cancer Using Intrinsic Susceptibility MRI. 

      Panek, R; Welsh, L; Baker, LCJ; Schmidt, MA; Wong, KH; Riddell, AM; Koh, D-M; Dunlop, A; Mcquaid, D; d'Arcy, JA; Bhide, SA; Harrington, KJ; Nutting, CM; Hopkinson, G; Richardson, C; Box, C; Eccles, SA; Leach, MO; Robinson, SP; Newbold, KL (2017-08)
      Purpose: To evaluate intrinsic susceptibility (IS) MRI for the identification of cycling hypoxia, and the assessment of its extent and spatial distribution, in head and neck squamous cell carcinoma (HNSCC) xenografts and ...
    • A novel serum protein signature associated with resistance to epidermal growth factor receptor tyrosine kinase inhibitors in head and neck squamous cell carcinoma. 

      Box, C; Mendiola, M; Gowan, S; Box, GM; Valenti, M; Brandon, ADH; Al-Lazikani, B; Rogers, SJ; Wilkins, A; Harrington, KJ; Eccles, SA (2013-07)
      BACKGROUND:Acquired resistance to tyrosine kinase inhibitors (TKIs) is becoming a major challenge in the treatment of many cancers. Epidermal growth factor receptor (EGFR) is overexpressed in squamous carcinomas, notably ...
    • Oncolytic reovirus as a combined antiviral and anti-tumour agent for the treatment of liver cancer. 

      Samson, A; Bentham, MJ; Scott, K; Nuovo, G; Bloy, A; Appleton, E; Adair, RA; Dave, R; Peckham-Cooper, A; Toogood, G; Nagamori, S; Coffey, M; Vile, R; Harrington, K; Selby, P; Errington-Mais, F; Melcher, A; Griffin, S (2018-03)
      OBJECTIVE:Oncolytic viruses (OVs) represent promising, proinflammatory cancer treatments. Here, we explored whether OV-induced innate immune responses could simultaneously inhibit HCV while suppressing hepatocellular ...
    • Oncolytic vaccinia virus as a vector for therapeutic sodium iodide symporter gene therapy in prostate cancer. 

      Mansfield, DC; Kyula, JN; Rosenfelder, N; Chao-Chu, J; Kramer-Marek, G; Khan, AA; Roulstone, V; McLaughlin, M; Melcher, AA; Vile, RG; Pandha, HS; Khoo, V; Harrington, KJ (2016-04)
      Oncolytic strains of vaccinia virus are currently in clinical development with clear evidence of safety and promising signs of efficacy. Addition of therapeutic genes to the viral genome may increase the therapeutic efficacy ...
    • The oncolytic virus Delta-24-RGD elicits an antitumor effect in pediatric glioma and DIPG mouse models. 

      Martínez-Vélez, N; Garcia-Moure, M; Marigil, M; González-Huarriz, M; Puigdelloses, M; Gallego Pérez-Larraya, J; Zalacaín, M; Marrodán, L; Varela-Guruceaga, M; Laspidea, V; Aristu, JJ; Ramos, LI; Tejada-Solís, S; Díez-Valle, R; Jones, C; Mackay, A; Martínez-Climent, JA; García-Barchino, MJ; Raabe, E; Monje, M; Becher, OJ; Junier, MP; El-Habr, EA; Chneiweiss, H; Aldave, G; Jiang, H; Fueyo, J; Patiño-García, A; Gomez-Manzano, C; Alonso, MM (2019-05-28)
      Pediatric high-grade glioma (pHGG) and diffuse intrinsic pontine gliomas (DIPGs) are aggressive pediatric brain tumors in desperate need of a curative treatment. Oncolytic virotherapy is emerging as a solid therapeutic ...
    • 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 ...
    • Phosphoproteomic Profiling Reveals ALK and MET as Novel Actionable Targets across Synovial Sarcoma Subtypes. 

      Fleuren, EDG; Vlenterie, M; van der Graaf, WTA; Hillebrandt-Roeffen, MHS; Blackburn, J; Ma, X; Chan, H; Magias, MC; van Erp, A; van Houdt, L; Cebeci, SAS; van de Ven, A; Flucke, UE; Heyer, EE; Thomas, DM; Lord, CJ; Marini, KD; Vaghjiani, V; Mercer, TR; Cain, JE; Wu, J; Versleijen-Jonkers, YMH; Daly, RJ (2017-08)
      Despite intensive multimodal treatment of sarcomas, a heterogeneous group of malignant tumors arising from connective tissue, survival remains poor. Candidate-based targeted treatments have demonstrated limited clinical ...