Now showing items 1-20 of 22

    • Accelerating drug development for neuroblastoma - New Drug Development Strategy: an Innovative Therapies for Children with Cancer, European Network for Cancer Research in Children and Adolescents and International Society of Paediatric Oncology Europe Neuroblastoma project. 

      Moreno, L; Caron, H; Geoerger, B; Eggert, A; Schleiermacher, G; Brock, P; Valteau-Couanet, D; Chesler, L; Schulte, JH; De Preter, K; Molenaar, J; Schramm, A; Eilers, M; Van Maerken, T; Johnsen, JI; Garrett, M; George, SL; Tweddle, DA; Kogner, P; Berthold, F; Koster, J; Barone, G; Tucker, ER; Marshall, L; Herold, R; Sterba, J; Norga, K; Vassal, G; Pearson, AD (2017-08)
      INTRODUCTION: Neuroblastoma, the commonest paediatric extra-cranial tumour, remains a leading cause of death from cancer in children. There is an urgent need to develop new drugs to improve cure rates and reduce long-term ...
    • 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 ...
    • Association with Aurora-A Controls N-MYC-Dependent Promoter Escape and Pause Release of RNA Polymerase II during the Cell Cycle. 

      Büchel, G; Carstensen, A; Mak, K-Y; Roeschert, I; Leen, E; Sumara, O; Hofstetter, J; Herold, S; Kalb, J; Baluapuri, A; Poon, E; Kwok, C; Chesler, L; Maric, HM; Rickman, DS; Wolf, E; Bayliss, R; Walz, S; Eilers, M (2017-12-19)
      MYC proteins bind globally to active promoters and promote transcriptional elongation by RNA polymerase II (Pol II). To identify effector proteins that mediate this function, we performed mass spectrometry on N-MYC complexes ...
    • Challenges to curing primary brain tumours. 

      Aldape, K; Brindle, KM; Chesler, L; Chopra, R; Gajjar, A; Gilbert, MR; Gottardo, N; Gutmann, DH; Hargrave, D; Holland, EC; Jones, DTW; Joyce, JA; Kearns, P; Kieran, MW; Mellinghoff, IK; Merchant, M; Pfister, SM; Pollard, SM; Ramaswamy, V; Rich, JN; Robinson, GW; Rowitch, DH; Sampson, JH; Taylor, MD; Workman, P; Gilbertson, RJ (2019-08)
      Despite decades of research, brain tumours remain among the deadliest of all forms of cancer. The ability of these tumours to resist almost all conventional and novel treatments relates, in part, to the unique cell-intrinsic ...
    • 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 ...
    • Designing Dual Inhibitors of Anaplastic Lymphoma Kinase (ALK) and Bromodomain-4 (BRD4) by Tuning Kinase Selectivity. 

      Watts, E; Heidenreich, D; Tucker, E; Raab, M; Strebhardt, K; Chesler, L; Knapp, S; Bellenie, B; Hoelder, S (2019-03-14)
      Concomitant inhibition of anaplastic lymphoma kinase (ALK) and bromodomain-4 (BRD4) is a potential therapeutic strategy for targeting two key oncogenic drivers that co-segregate in a significant fraction of high-risk ...
    • Development of a targeted sequencing approach to identify prognostic, predictive and diagnostic markers in paediatric solid tumours. 

      Izquierdo, E; Yuan, L; George, S; Hubank, M; Jones, C; Proszek, P; Shipley, J; Gatz, SA; Stinson, C; Moore, AS; Clifford, SC; Hicks, D; Lindsey, JC; Hill, RM; Jacques, TS; Chalker, J; Thway, K; O'Connor, S; Marshall, L; Moreno, L; Pearson, A; Chesler, L; Walker, BA; De Castro, DG (2017-12-19)
      The implementation of personalised medicine in childhood cancers has been limited by a lack of clinically validated multi-target sequencing approaches specific for paediatric solid tumours. In order to support innovative ...
    • Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma. 

      Zeid, R; Lawlor, MA; Poon, E; Reyes, JM; Fulciniti, M; Lopez, MA; Scott, TG; Nabet, B; Erb, MA; Winter, GE; Jacobson, Z; Polaski, DR; Karlin, KL; Hirsch, RA; Munshi, NP; Westbrook, TF; Chesler, L; Lin, CY; Bradner, JE (2018-04)
      Amplification of the locus encoding the oncogenic transcription factor MYCN is a defining feature of high-risk neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of MYCN perturbation ...
    • From class waivers to precision medicine in paediatric oncology. 

      Pearson, ADJ; Pfister, SM; Baruchel, A; Bourquin, J-P; Casanova, M; Chesler, L; Doz, F; Eggert, A; Geoerger, B; Jones, DTW; Kearns, PR; Molenaar, JJ; Morland, B; Schleiermacher, G; Schulte, JH; Vormoor, J; Marshall, LV; Zwaan, CM; Vassal, G; Executive and Biology Committees of the Innovative Therapies for Children with Cancer European Consortium (2017-07)
      New drugs are crucially needed for children with cancer. The European Paediatric Regulation facilitates paediatric class waivers for drugs developed for diseases only occurring in adults. In this Review, we retrospectively ...
    • Glycogen synthase kinase 3 controls migration of the neural crest lineage in mouse and Xenopus. 

      Gonzalez Malagon, SG; Lopez Muñoz, AM; Doro, D; Bolger, TG; Poon, E; Tucker, ER; Adel Al-Lami, H; Krause, M; Phiel, CJ; Chesler, L; Liu, KJ (2018-03-19)
      Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report ...
    • Immunoassays for the quantification of ALK and phosphorylated ALK support the evaluation of on-target ALK inhibitors in neuroblastoma. 

      Tucker, ER; Tall, JR; Danielson, LS; Gowan, S; Jamin, Y; Robinson, SP; Banerji, U; Chesler, L (2017-08)
      Targeted inhibition of anaplastic lymphoma kinase (ALK) is a successful approach for the treatment of many ALK-aberrant malignancies; however, the presence of resistant mutations necessitates both the development of more ...
    • In vivo modelling of chemo-resistant neuroblastoma provides new insights into chemo-refractory disease and metastasis. 

      Yogev, O; Almeida, GS; Barker, KT; George, SL; Kwok, C; Campbell, J; Zarowiecki, M; Kleftogiannis, D; Smith, LM; Hallsworth, A; Berry, P; Möcklinghoff, T; Webber, HT; Danielson, LS; Buttery, B; Calton, EA; da Costa, BM; Poon, E; Jamin, Y; Lise, S; Veal, GJ; Sebire, N; Robinson, SP; Anderson, J; Chesler, L (2019-08-12)
      Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant in vivo models has limited our insight into the development ...
    • Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors. 

      Vaughan, L; Clarke, PA; Barker, K; Chanthery, Y; Gustafson, CW; Tucker, E; Renshaw, J; Raynaud, F; Li, X; Burke, R; Jamin, Y; Robinson, SP; Pearson, A; Maira, M; Weiss, WA; Workman, P; Chesler, L (2016-07-12)
      MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ...
    • Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Non-invasive Magnetic Resonance Elastography. 

      Li, J; Zormpas-Petridis, K; Boult, JK; Reeves, EL; Heindl, A; Vinci, M; Lopes, F; Cummings, C; Springer, CJ; Chesler, L; Jones, C; Bamber, JC; Yuan, Y; Sinkus, R; Jamin, Y; Robinson, SP (2019-10-11)
      Increased stiffness in the extracellular matrix (ECM) contributes to tumor progression and metastasis. Therefore, stromal modulating therapies and accompanying biomarkers are being developed to target ECM stiffness. Magnetic ...
    • Macrophage-Derived IL1β and TNFα Regulate Arginine Metabolism in Neuroblastoma. 

      Fultang, L; Gamble, LD; Gneo, L; Berry, AM; Egan, SA; De Bie, F; Yogev, O; Eden, GL; Booth, S; Brownhill, S; Vardon, A; McConville, CM; Cheng, PN; Norris, MD; Etchevers, HC; Murray, J; Ziegler, DS; Chesler, L; Schmidt, R; Burchill, SA; Haber, M; De Santo, C; Mussai, F (2019-02-01)
      Neuroblastoma is the most common childhood solid tumor, yet the prognosis for high-risk disease remains poor. We demonstrate here that arginase 2 (ARG2) drives neuroblastoma cell proliferation via regulation of arginine ...
    • MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment. 

      Zormpas-Petridis, K; Jerome, NP; Blackledge, MD; Carceller, F; Poon, E; Clarke, M; McErlean, CM; Barone, G; Koers, A; Vaidya, SJ; Marshall, LV; Pearson, ADJ; Moreno, L; Anderson, J; Sebire, N; McHugh, K; Koh, D-M; Yuan, Y; Chesler, L; Robinson, SP; Jamin, Y (2019-06-01)
      Childhood neuroblastoma is a hypervascular tumor of neural origin, for which antiangiogenic drugs are currently being evaluated; however, predictive biomarkers of treatment response, crucial for successful delivery of ...
    • p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance. 

      Yogev, O; Barker, K; Sikka, A; Almeida, GS; Hallsworth, A; Smith, LM; Jamin, Y; Ruddle, R; Koers, A; Webber, HT; Raynaud, FI; Popov, S; Jones, C; Petrie, K; Robinson, SP; Keun, HC; Chesler, L (2016-05)
      Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ...
    • Pre-clinical imaging of transgenic mouse models of neuroblastoma using a dedicated 3-element solenoid coil on a clinical 3T platform. 

      Almeida, GS; Panek, R; Hallsworth, A; Webber, H; Papaevangelou, E; Boult, JK; Jamin, Y; Chesler, L; Robinson, SP (2017-09-05)
      BACKGROUND: The use of clinical MRI scanners to conduct pre-clinical research facilitates comparisons with clinical studies. Here the utility and sensitivity of anatomical and functional MRI data/biomarkers acquired from ...
    • Preclinical transgenic and patient-derived xenograft models recapitulate the radiological features of human adamantinomatous craniopharyngioma. 

      Boult, JKR; Apps, JR; Hölsken, A; Hutchinson, JC; Carreno, G; Danielson, LS; Smith, LM; Bäuerle, T; Buslei, R; Buchfelder, M; Virasami, AK; Koers, A; Arthurs, OJ; Jacques, TS; Chesler, L; Martinez-Barbera, JP; Robinson, SP (2018-07)
      To assess the clinical relevance of transgenic and patient-derived xenograft models of adamantinomatous craniopharyngioma (ACP) using serial magnetic resonance imaging (MRI) and high resolution post-mortem microcomputed ...
    • SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma. 

      Carreno, G; Boult, JKR; Apps, JR; Gonzalez-Meljem, JM; Haston, S; Guiho, R; Stache, C; Danielson, LS; Koers, A; Smith, LS; Virasami, A; Panousopoulos, L; Buchfelder, M; Jacques, TS; Chesler, L; Robinson, S; Martinez-Barbera, JP (2019-01-01)
      Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children ...