Now showing items 1-20 of 35

    • A tailored molecular profiling programme for children with cancer to identify clinically actionable genetic alterations. 

      George, SL; Izquierdo, E; Campbell, J; Koutroumanidou, E; Proszek, P; Jamal, S; Hughes, D; Yuan, L; Marshall, LV; Carceller, F; Chisholm, JC; Vaidya, S; Mandeville, H; Angelini, P; Wasti, A; Bexelius, T; Thway, K; Gatz, SA; Clarke, M; Al-Lazikani, B; Barone, G; Anderson, J; Tweddle, DA; Gonzalez, D; Walker, BA; Barton, J; Depani, S; Eze, J; Ahmed, SW; Moreno, L; Pearson, A; Shipley, J; Jones, C; Hargrave, D; Jacques, TS; Hubank, M; Chesler, L (2019-11)
      BACKGROUND:For children with cancer, the clinical integration of precision medicine to enable predictive biomarker-based therapeutic stratification is urgently needed. METHODS:We have developed a hybrid-capture next-generation ...
    • 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 ...
    • 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)
      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 ...
    • Combined MYC and P53 defects emerge at medulloblastoma relapse and define rapidly progressive, therapeutically targetable disease. 

      Hill, RM; Kuijper, S; Lindsey, JC; Petrie, K; Schwalbe, EC; Barker, K; Boult, JKR; Williamson, D; Ahmad, Z; Hallsworth, A; Ryan, SL; Poon, E; Robinson, SP; Ruddle, R; Raynaud, FI; Howell, L; Kwok, C; Joshi, A; Nicholson, SL; Crosier, S; Ellison, DW; Wharton, SB; Robson, K; Michalski, A; Hargrave, D; Jacques, TS; Pizer, B; Bailey, S; Swartling, FJ; Weiss, WA; Chesler, L; Clifford, SC (2015-01)
      We undertook a comprehensive clinical and biological investigation of serial medulloblastoma biopsies obtained at diagnosis and relapse. Combined MYC family amplifications and P53 pathway defects commonly emerged at relapse, ...
    • 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 ...
    • 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)
      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 (2017-12-06)
      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 ...
    • Frequency and Prognostic Impact of <i>ALK</i> Amplifications and Mutations in the European Neuroblastoma Study Group (SIOPEN) High-Risk Neuroblastoma Trial (HR-NBL1). 

      Bellini, A; Pötschger, U; Bernard, V; Lapouble, E; Baulande, S; Ambros, PF; Auger, N; Beiske, K; Bernkopf, M; Betts, DR; Bhalshankar, J; Bown, N; de Preter, K; Clément, N; Combaret, V; Font de Mora, J; George, SL; Jiménez, I; Jeison, M; Marques, B; Martinsson, T; Mazzocco, K; Morini, M; Mühlethaler-Mottet, A; Noguera, R; Pierron, G; Rossing, M; Taschner-Mandl, S; Van Roy, N; Vicha, A; Chesler, L; Balwierz, W; Castel, V; Elliott, M; Kogner, P; Laureys, G; Luksch, R; Malis, J; Popovic-Beck, M; Ash, S; Delattre, O; Valteau-Couanet, D; Tweddle, DA; Ladenstein, R; Schleiermacher, G (2021-06-11)
      Purpose In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied <i>ALK</i> genetic alterations in high-risk (HR) ...
    • 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 ...
    • Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium. 

      Shern, JF; Selfe, J; Izquierdo, E; Patidar, R; Chou, H-C; Song, YK; Yohe, ME; Sindiri, S; Wei, J; Wen, X; Rudzinski, ER; Barkauskas, DA; Lo, T; Hall, D; Linardic, CM; Hughes, D; Jamal, S; Jenney, M; Chisholm, J; Brown, R; Jones, K; Hicks, B; Angelini, P; George, S; Chesler, L; Hubank, M; Kelsey, A; Gatz, SA; Skapek, SX; Hawkins, DS; Shipley, JM; Khan, J
      Purpose Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Despite aggressive therapy, the 5-year survival rate for patients with metastatic or recurrent disease remains poor, and beyond <i>PAX-FOXO1</i> ...
    • 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 ...
    • <i>In Vivo</i> Modeling of Chemoresistant Neuroblastoma Provides New Insights into Chemorefractory 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 (2019-10)
      Neuroblastoma is a pediatric cancer that is frequently metastatic and resistant to conventional treatment. In part, a lack of natively metastatic, chemoresistant <i>in vivo</i> models has limited our insight into the ...
    • 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 ...
    • 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 (2016-09)
      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 ...
    • Intrinsic susceptibility MRI identifies tumors with ALKF1174L mutation in genetically-engineered murine models of high-risk neuroblastoma. 

      Jamin, Y; Glass, L; Hallsworth, A; George, R; Koh, D-M; Pearson, ADJ; Chesler, L; Robinson, SP (2014-01)
      The early identification of children presenting ALK(F1174L)-mutated neuroblastoma, which are associated with resistance to the promising ALK inhibitor crizotinib and a marked poorer prognosis, has become a clinical priority. ...
    • Investigating the Contribution of Collagen to the Tumor Biomechanical Phenotype with Noninvasive Magnetic Resonance Elastography. 

      Li, J; Zormpas-Petridis, K; Boult, JKR; 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 (2019-11)
      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)
      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)
      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 ...