Browsing ICR Divisions by author "Chesler, Louis"
Now showing items 1-20 of 44
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18F-meta-fluorobenzylguanidine (18F-mFBG) to monitor changes in norepinephrine transporter expression in response to therapeutic intervention in neuroblastoma models.
Turnock, S; Turton, DR; Martins, CD; Chesler, L; Wilson, TC; et al. (NATURE PORTFOLIO, 2020-12-01)Targeted radiotherapy with 131I-mIBG, a substrate of the human norepinephrine transporter (NET-1), shows promising responses in heavily pre-treated neuroblastoma (NB) patients. Combinatorial approaches that enhance 131I-mIBG ... -
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; et al. (ELSEVIER SCI LTD, 2019-11-01)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: Summary of the Second Neuroblastoma Drug Development Strategy forum from Innovative Therapies for Children with Cancer and International Society of Paediatric Oncology Europe Neuroblastoma.
Moreno, L; Barone, G; DuBois, SG; Molenaar, J; Fischer, M; et al. (ELSEVIER SCI LTD, 2020-09-01)Only one class of targeted agents (anti-GD2 antibodies) has been incorporated into front-line therapy for neuroblastoma since the 1980s. The Neuroblastoma New Drug Development Strategy (NDDS) initiative commenced in 2012 ... -
Biological Role of MYCN in Medulloblastoma: Novel Therapeutic Opportunities and Challenges Ahead.
Shrestha, S; Morcavallo, A; Gorrini, C; Chesler, L (FRONTIERS MEDIA SA, 2021-06-14)The constitutive and dysregulated expression of the transcription factor MYCN has a central role in the pathogenesis of the paediatric brain tumour medulloblastoma, with an increased expression of this oncogene correlating ... -
Bromodomain and extra-terminal inhibitors-A consensus prioritisation after the Paediatric Strategy Forum for medicinal product development of epigenetic modifiers in children-ACCELERATE.
Pearson, AD; DuBois, SG; Buenger, V; Kieran, M; Stegmaier, K; et al. (ELSEVIER SCI LTD, 2021-02-16)Based on biology and pre-clinical data, bromodomain and extra-terminal (BET) inhibitors have at least three potential roles in paediatric malignancies: NUT (nuclear protein in testis) carcinomas, MYC/MYCN-driven cancers and ... -
Challenges to curing primary brain tumours.
Aldape, K; Brindle, KM; Chesler, L; Chopra, R; Gajjar, A; et al. (NATURE PUBLISHING GROUP, 2019-08-01)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 ... -
Circulating tumour DNA sequencing to determine therapeutic response and identify tumour heterogeneity in patients with paediatric solid tumours.
Stankunaite, R; George, SL; Gallagher, L; Jamal, S; Shaikh, R; et al. (ELSEVIER SCI LTD, 2021-12-18)OBJECTIVE: Clinical diagnostic sequencing of circulating tumour DNA (ctDNA) is well advanced for adult patients, but application to paediatric cancer patients lags behind. METHODS: To address this, we have developed a ... -
Combination Therapies Targeting ALK-aberrant Neuroblastoma in Preclinical Models.
Tucker, ER; Jiménez, I; Chen, L; Bellini, A; Gorrini, C; et al. (AMER ASSOC CANCER RESEARCH, 2023-04-03)PURPOSE: ALK-activating mutations are identified in approximately 10% of newly diagnosed neuroblastomas and ALK amplifications in a further 1%-2% of cases. Lorlatinib, a third-generation anaplastic lymphoma kinase (ALK) ... -
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; et al. (CELL PRESS, 2015-01-12)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; et al. (AMER ASSOC CANCER RESEARCH, 2015-11-15)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; et al. (AMER CHEMICAL SOC, 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 ... -
Dual inhibition of EZH2 and G9A/GLP histone methyltransferases by HKMTI-1-005 promotes differentiation of acute myeloid leukemia cells.
Sbirkov, Y; Schenk, T; Kwok, C; Stengel, S; Brown, R; et al. (FRONTIERS MEDIA SA, 2023-03-23)All-trans-retinoic acid (ATRA)-based differentiation therapy of acute promyelocytic leukemia (APL) represents one of the most clinically effective examples of precision medicine and the first example of targeted oncoprotein ... -
Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma.
Zeid, R; Lawlor, MA; Poon, E; Reyes, JM; Fulciniti, M; et al. (NATURE PUBLISHING GROUP, 2018-04-01)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 ALK 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; et al. (LIPPINCOTT WILLIAMS & WILKINS, 2021-10-20)PURPOSE: In neuroblastoma (NB), the ALK receptor tyrosine kinase can be constitutively activated through activating point mutations or genomic amplification. We studied ALK genetic alterations in high-risk (HR) patients ... -
Genomic Classification and Clinical Outcome in Rhabdomyosarcoma: A Report From an International Consortium.
Shern, JF; Selfe, J; Izquierdo, E; Patidar, R; Chou, H-C; et al. (LIPPINCOTT WILLIAMS & WILKINS, 2021-09-10)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 PAX-FOXO1 fusion ... -
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; et al. (NATURE PUBLISHING GROUP, 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; et al. (WILEY, 2017-08-01)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 Modeling of Chemoresistant Neuroblastoma Provides New Insights into Chemorefractory Disease and Metastasis.
Yogev, O; Almeida, GS; Barker, KT; George, SL; Kwok, C; et al. (AMER ASSOC CANCER RESEARCH, 2019-10-15)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 ... -
Indisulam targets RNA splicing and metabolism to serve as a therapeutic strategy for high-risk neuroblastoma.
Nijhuis, A; Sikka, A; Yogev, O; Herendi, L; Balcells, C; et al. (NATURE PORTFOLIO, 2022-03-16)Neuroblastoma is the most common paediatric solid tumour and prognosis remains poor for high-risk cases despite the use of multimodal treatment. Analysis of public drug sensitivity data showed neuroblastoma lines to be ... -
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; et al. (IMPACT JOURNALS LLC, 2016-09-06)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 ...