Now showing items 1-20 of 79

    • A Biobank of Breast Cancer Explants with Preserved Intra-tumor Heterogeneity to Screen Anticancer Compounds. 

      Bruna, A; Rueda, OM; Greenwood, W; Batra, AS; Callari, M; Batra, RN; Pogrebniak, K; Sandoval, J; Cassidy, JW; Tufegdzic-Vidakovic, A; Sammut, S-J; Jones, L; Provenzano, E; Baird, R; Eirew, P; Hadfield, J; Eldridge, M; McLaren-Douglas, A; Barthorpe, A; Lightfoot, H; O'Connor, MJ; Gray, J; Cortes, J; Baselga, J; Marangoni, E; Welm, AL; Aparicio, S; Serra, V; Garnett, MJ; Caldas, C (2016-09-15)
      The inter- and intra-tumor heterogeneity of breast cancer needs to be adequately captured in pre-clinical models. We have created a large collection of breast cancer patient-derived tumor xenografts (PDTXs), in which the ...
    • A new method for the high-precision assessment of tumor changes in response to treatment. 

      Tar, PD; Thacker, NA; Babur, M; Watson, Y; Cheung, S; Little, RA; Gieling, RG; Williams, KJ; O'Connor, JPB (2018-08)
      Motivation:Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The ...
    • 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 ...
    • Achieving In Vivo Target Depletion through the Discovery and Optimization of Benzimidazolone BCL6 Degraders. 

      Bellenie, BR; Cheung, K-MJ; Varela, A; Pierrat, OA; Collie, GW; Box, GM; Bright, MD; Gowan, S; Hayes, A; Rodrigues, MJ; Shetty, KN; Carter, M; Davis, OA; Henley, AT; Innocenti, P; Johnson, LD; Liu, M; de Klerk, S; Le Bihan, Y-V; Lloyd, MG; McAndrew, PC; Shehu, E; Talbot, R; Woodward, HL; Burke, R; Kirkin, V; van Montfort, RLM; Raynaud, FI; Rossanese, OW; Hoelder, S (2020-04-10)
      Deregulation of the transcriptional repressor BCL6 enables tumorigenesis of germinal center B-cells, and hence BCL6 has been proposed as a therapeutic target for the treatment of diffuse large B-cell lymphoma (DLBCL). ...
    • Activation of MAPK Signaling by CXCR7 Leads to Enzalutamide Resistance in Prostate Cancer. 

      Li, S; Fong, K-W; Gritsina, G; Zhang, A; Zhao, JC; Kim, J; Sharp, A; Yuan, W; Aversa, C; Yang, XJ; Nelson, PS; Feng, FY; Chinnaiyan, AM; de Bono, JS; Morrissey, C; Rettig, MB; Yu, J (2019-05)
      Castration-resistant prostate cancer (CRPC) that has developed resistance to the new-generation androgen receptor (AR) antagonist enzalutamide is a lethal disease. Transcriptome analysis of multiple prostate cancer models ...
    • Acute tumour response to a bispecific Ang-2-VEGF-A antibody: insights from multiparametric MRI and gene expression profiling. 

      Baker, LCJ; Boult, JKR; Thomas, M; Koehler, A; Nayak, T; Tessier, J; Ooi, C-H; Birzele, F; Belousov, A; Zajac, M; Horn, C; LeFave, C; Robinson, SP (2016-09)
      Background To assess antivascular effects, and evaluate clinically translatable magnetic resonance imaging (MRI) biomarkers of tumour response in vivo, following treatment with vanucizumab, a bispecific human antibody ...
    • ALK2 inhibitors display beneficial effects in preclinical models of <i>ACVR1</i> mutant diffuse intrinsic pontine glioma. 

      Carvalho, D; Taylor, KR; Olaciregui, NG; Molinari, V; Clarke, M; Mackay, A; Ruddle, R; Henley, A; Valenti, M; Hayes, A; Brandon, ADH; Eccles, SA; Raynaud, F; Boudhar, A; Monje, M; Popov, S; Moore, AS; Mora, J; Cruz, O; Vinci, M; Brennan, PE; Bullock, AN; Carcaboso, AM; Jones, C (2019-01)
      Diffuse intrinsic pontine glioma (DIPG) is a lethal childhood brainstem tumour, with a quarter of patients harbouring somatic mutations in <i>ACVR1</i>, encoding the serine/threonine kinase ALK2. Despite being an amenable ...
    • Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer. 

      Sharp, A; Coleman, I; Yuan, W; Sprenger, C; Dolling, D; Rodrigues, DN; Russo, JW; Figueiredo, I; Bertan, C; Seed, G; Riisnaes, R; Uo, T; Neeb, A; Welti, J; Morrissey, C; Carreira, S; Luo, J; Nelson, PS; Balk, SP; True, LD; de Bono, JS; Plymate, SR (2019-01)
      Background Liquid biopsies have demonstrated that the constitutively active androgen receptor splice variant-7 (AR-V7) associates with reduced response and overall survival from endocrine therapies in castration-resistant ...
    • 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)
      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. ...
    • Application of Sequencing, Liquid Biopsies, and Patient-Derived Xenografts for Personalized Medicine in Melanoma. 

      Girotti, MR; Gremel, G; Lee, R; Galvani, E; Rothwell, D; Viros, A; Mandal, AK; Lim, KHJ; Saturno, G; Furney, SJ; Baenke, F; Pedersen, M; Rogan, J; Swan, J; Smith, M; Fusi, A; Oudit, D; Dhomen, N; Brady, G; Lorigan, P; Dive, C; Marais, R (2016-03)
      Unlabelled Targeted therapies and immunotherapies have transformed melanoma care, extending median survival from ∼9 to over 25 months, but nevertheless most patients still die of their disease. The aim of precision medicine ...
    • ARID1A influences HDAC1/BRD4 activity, intrinsic proliferative capacity and breast cancer treatment response. 

      Nagarajan, S; Rao, SV; Sutton, J; Cheeseman, D; Dunn, S; Papachristou, EK; Prada, J-EG; Couturier, D-L; Kumar, S; Kishore, K; Chilamakuri, CSR; Glont, S-E; Archer Goode, E; Brodie, C; Guppy, N; Natrajan, R; Bruna, A; Caldas, C; Russell, A; Siersbæk, R; Yusa, K; Chernukhin, I; Carroll, JS
      Using genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screens to understand endocrine drug resistance, we discovered ARID1A and other SWI/SNF complex components as the factors most critically ...
    • ATR Inhibition Potentiates the Radiation-induced Inflammatory Tumor Microenvironment. 

      Dillon, MT; Bergerhoff, KF; Pedersen, M; Whittock, H; Crespo-Rodriguez, E; Patin, EC; Pearson, A; Smith, HG; Paget, JTE; Patel, RR; Foo, S; Bozhanova, G; Ragulan, C; Fontana, E; Desai, K; Wilkins, AC; Sadanandam, A; Melcher, A; McLaughlin, M; Harrington, KJ (2019-06)
      Purpose ATR inhibitors (ATRi) are in early phase clinical trials and have been shown to sensitize to chemotherapy and radiotherapy preclinically. Limited data have been published about the effect of these drugs on the tumor ...
    • 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)
      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 ...
    • BRCA1 and BRCA2 tumor suppressors protect against endogenous acetaldehyde toxicity. 

      Tacconi, EM; Lai, X; Folio, C; Porru, M; Zonderland, G; Badie, S; Michl, J; Sechi, I; Rogier, M; Matía García, V; Batra, AS; Rueda, OM; Bouwman, P; Jonkers, J; Ryan, A; Reina-San-Martin, B; Hui, J; Tang, N; Bruna, A; Biroccio, A; Tarsounas, M (2017-10)
      Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source ...
    • BRD4 facilitates replication stress-induced DNA damage response. 

      Zhang, J; Dulak, AM; Hattersley, MM; Willis, BS; Nikkilä, J; Wang, A; Lau, A; Reimer, C; Zinda, M; Fawell, SE; Mills, GB; Chen, H (2018-07)
      Previous reports have demonstrated that select cancers depend on BRD4 to regulate oncogenic gene transcriptional programs. Here we describe a novel role for BRD4 in DNA damage response (DDR). BRD4 associates with and ...
    • 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 (2017-01)
      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 ...
    • Cells Lacking the <i>RB1</i> Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. 

      Oser, MG; Fonseca, R; Chakraborty, AA; Brough, R; Spektor, A; Jennings, RB; Flaifel, A; Novak, JS; Gulati, A; Buss, E; Younger, ST; McBrayer, SK; Cowley, GS; Bonal, DM; Nguyen, Q-D; Brulle-Soumare, L; Taylor, P; Cairo, S; Ryan, CJ; Pease, EJ; Maratea, K; Travers, J; Root, DE; Signoretti, S; Pellman, D; Ashton, S; Lord, CJ; Barry, ST; Kaelin, WG (2019-02)
      Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating <i>RB1</i> and <i>TP53</i> mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical ...
    • 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)
      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 prevents ...
    • CHK1 Inhibition Radiosensitizes Head and Neck Cancers to Paclitaxel-Based Chemoradiotherapy. 

      Barker, HE; Patel, R; McLaughlin, M; Schick, U; Zaidi, S; Nutting, CM; Newbold, KL; Bhide, S; Harrington, KJ (2016-09)
      Head and neck squamous cell carcinoma (HNSCC) is a leading cause of cancer-related deaths, with increasingly more cases arising due to high-risk human papillomavirus (HPV) infection. Cisplatin-based chemoradiotherapy is a ...