Now showing items 1-20 of 30

    • Androgen Receptor Variants Mediate DNA Repair after Prostate Cancer Irradiation. 

      Yin, Y; Li, R; Xu, K; Ding, S; Li, J; Baek, G; Ramanand, SG; Ding, S; Liu, Z; Gao, Y; Kanchwala, MS; Li, X; Hutchinson, R; Liu, X; Woldu, SL; Xing, C; Desai, NB; Feng, FY; Burma, S; de Bono, JS; Dehm, SM; Mani, RS; Chen, BPC; Raj, GV (2017-09-15)
      In prostate cancer, androgen deprivation therapy (ADT) enhances the cytotoxic effects of radiotherapy. This effect is associated with weakening of the DNA damage response (DDR) normally supported by the androgen receptor. ...
    • 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 ...
    • Cationic lipid-based nanoparticles mediate functional delivery of acetate to tumor cells in vivo leading to significant anticancer effects. 

      Brody, LP; Sahuri-Arisoylu, M; Parkinson, JR; Parkes, HG; So, PW; Hajji, N; Thomas, EL; Frost, GS; Miller, AD; Bell, JD (2017)
      Metabolic reengineering using nanoparticle delivery represents an innovative therapeutic approach to normalizing the deregulation of cellular metabolism underlying many diseases, including cancer. Here, we demonstrated a ...
    • CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
      Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
    • 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 ...
    • Correlation of Ultrasound Shear Wave Elastography with Pathological Analysis in a Xenografic Tumour Model. 

      Elyas, E; Papaevangelou, E; Alles, EJ; Erler, JT; Cox, TR; Robinson, SP; Bamber, JC (2017-03-13)
      The objective of this study was to evaluate the potential value of ultrasound (US) shear wave elastography (SWE) in assessing the relative change in elastic modulus in colorectal adenocarcinoma xenograft models in vivo and ...
    • Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. 

      Dolman, ME; Poon, E; Ebus, ME; den Hartog, IJ; van Noesel, CJ; Jamin, Y; Hallsworth, A; Robinson, SP; Petrie, K; Sparidans, RW; Kok, RJ; Versteeg, R; Caron, HN; Chesler, L; Molenaar, JJ (2015-11)
      MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted inhibition ...
    • EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer. 

      Oldrini, B; Hsieh, W-Y; Erdjument-Bromage, H; Codega, P; Carro, MS; Curiel-García, A; Campos, C; Pourmaleki, M; Grommes, C; Vivanco, I; Rohle, D; Bielski, CM; Taylor, BS; Hollmann, TJ; Rosenblum, M; Tempst, P; Blenis, J; Squatrito, M; Mellinghoff, IK (2017-12-11)
      Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains ...
    • Evaluation of the Response of Intracranial Xenografts to VEGF Signaling Inhibition Using Multiparametric MRI. 

      Boult, JKR; Box, G; Vinci, M; Perryman, L; Eccles, SA; Jones, C; Robinson, SP (2017-09)
      Vascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic ...
    • 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 ...
    • 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 (2017-11-01)
      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 ...
    • 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 (2017-08-01)
      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 (2018-06-01)
      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, ES; 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 (2017-08-01)
      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 ...