Now showing items 1-18 of 18

    • 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 ...
    • 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. ...
    • 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 ...
    • CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. 

      Zimmermann, M; Murina, O; Reijns, MAM; Agathanggelou, A; Challis, R; Tarnauskaitė, Ž; Muir, M; Fluteau, A; Aregger, M; McEwan, A; Yuan, W; Clarke, M; Lambros, MB; Paneesha, S; Moss, P; Chandrashekhar, M; Angers, S; Moffat, J; Brunton, VG; Hart, T; de Bono, J; Stankovic, T; Jackson, AP; Durocher, D (2018-07-04)
      The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in ...
    • Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. 

      Dolman, MEM; Poon, E; Ebus, ME; den Hartog, IJM; van Noesel, CJM; Jamin, Y; Hallsworth, A; Robinson, SP; Petrie, K; Sparidans, RW; Kok, RJ; Versteeg, R; Caron, HN; Chesler, L; Molenaar, JJ (2015-11)
      PURPOSE: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 ...
    • Detection of circulating tumour cell clusters in human glioblastoma. 

      Krol, I; Castro-Giner, F; Maurer, M; Gkountela, S; Szczerba, BM; Scherrer, R; Coleman, N; Carreira, S; Bachmann, F; Anderson, S; Engelhardt, M; Lane, H; Evans, TRJ; Plummer, R; Kristeleit, R; Lopez, J; Aceto, N (2018-08)
      Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular ...
    • 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 ...
    • 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 ...
    • 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 ...
    • 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 ...
    • 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 ...
    • 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 ...
    • PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer. 

      Brasó-Maristany, F; Filosto, S; Catchpole, S; Marlow, R; Quist, J; Francesch-Domenech, E; Plumb, DA; Zakka, L; Gazinska, P; Liccardi, G; Meier, P; Gris-Oliver, A; Cheang, MCU; Perdrix-Rosell, A; Shafat, M; Noël, E; Patel, N; McEachern, K; Scaltriti, M; Castel, P; Noor, F; Buus, R; Mathew, S; Watkins, J; Serra, V; Marra, P; Grigoriadis, A; Tutt, AN (2016-11)
      Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC ...
    • Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma. 

      Bridgeman, VL; Wan, E; Foo, S; Nathan, MR; Welti, JC; Frentzas, S; Vermeulen, PB; Preece, N; Springer, CJ; Powles, T; Nathan, PD; Larkin, J; Gore, M; Vasudev, NS; Reynolds, AR (2016-01)
      Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this ...
    • Second-Generation HSP90 Inhibitor Onalespib Blocks mRNA Splicing of Androgen Receptor Variant 7 in Prostate Cancer Cells. 

      Ferraldeschi, R; Welti, J; Powers, MV; Yuan, W; Smyth, T; Seed, G; Riisnaes, R; Hedayat, S; Wang, H; Crespo, M; Nava Rodrigues, D; Figueiredo, I; Miranda, S; Carreira, S; Lyons, JF; Sharp, S; Plymate, SR; Attard, G; Wallis, N; Workman, P; de Bono, JS (2016-05)
      Resistance to available hormone therapies in prostate cancer has been associated with alternative splicing of androgen receptor (AR) and specifically, the expression of truncated and constitutively active AR variant 7 ...
    • Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer. 

      Wagner, S; Vlachogiannis, G; De Haven Brandon, A; Valenti, M; Box, G; Jenkins, L; Mancusi, C; Self, A; Manodoro, F; Assiotis, I; Robinson, P; Chauhan, R; Rust, AG; Matthews, N; Eason, K; Khan, K; Starling, N; Cunningham, D; Sadanandam, A; Isacke, CM; Kirkin, V; Valeri, N; Whittaker, SR (2019-03)
      Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...