Now showing items 1-12 of 12

    • 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)
      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 ...
    • 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 ...
    • 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 ...
    • In Vivo 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 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 (2016-09)
      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. ...
    • 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 ...
    • 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)
      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 transgenic ...
    • Structural basis of N-Myc binding by Aurora-A and its destabilization by kinase inhibitors. 

      Richards, MW; Burgess, SG; Poon, E; Carstensen, A; Eilers, M; Chesler, L; Bayliss, R (2016-11-11)
      Myc family proteins promote cancer by inducing widespread changes in gene expression. Their rapid turnover by the ubiquitin-proteasome pathway is regulated through phosphorylation of Myc Box I and ubiquitination by the E3 ...