Browsing Cancer Therapeutics by author "Robinson, Simon"
Now showing items 1-20 of 27
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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 ... -
Detection of the prodrug-activating enzyme carboxypeptidase G2 activity with chemical exchange saturation transfer magnetic resonance.
Jamin, Y; Eykyn, TR; Poon, E; Springer, CJ; Robinson, SP (SPRINGER, 2014-04-01)PURPOSE: The purpose of this study is to evaluate if the differential exchange rates with bulk water between amine and amide protons can be exploited using chemical exchange saturation transfer magnetic resonance (CEST-MR) ... -
DIPG Harbors Alterations Targetable by MEK Inhibitors, with Acquired Resistance Mechanisms Overcome by Combinatorial Inhibition.
Izquierdo, E; Carvalho, DM; Mackay, A; Temelso, S; Boult, JKR; et al. (AMER ASSOC CANCER RESEARCH, 2022-03-01)UNLABELLED: The survival of children with diffuse intrinsic pontine glioma (DIPG) remains dismal, with new treatments desperately needed. In a prospective biopsy-stratified clinical trial, we combined detailed molecular ... -
Evaluating Imaging Biomarkers of Acquired Resistance to Targeted EGFR Therapy in Xenograft Models of Human Head and Neck Squamous Cell Carcinoma.
Baker, LCJ; Sikka, A; Price, JM; Boult, JKR; Lepicard, EY; et al. (FRONTIERS MEDIA SA, 2018-07-23)Background: Overexpression of EGFR is a negative prognostic factor in head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC who respond to EGFR-targeted tyrosine kinase inhibitors (TKIs) eventually develop ... -
Evaluation of the Response of Intracranial Xenografts to VEGF Signaling Inhibition Using Multiparametric MRI.
Boult, JKR; Box, G; Vinci, M; Perryman, L; Eccles, SA; et al. (ELSEVIER SCIENCE INC, 2017-09-01)Vascular endothelial growth factor A (VEGF-A) is considered one of the most important factors in tumor angiogenesis, and consequently, a number of therapeutics have been developed to inhibit VEGF signaling. Therapeutic ... -
Hypoxia and its therapeutic possibilities in paediatric cancers.
Bernauer, C; Man, YKS; Chisholm, JC; Lepicard, EY; Robinson, SP; et al. (SPRINGERNATURE, 2021-02-02)In tumours, hypoxia-a condition in which the demand for oxygen is higher than its availability-is well known to be associated with reduced sensitivity to radiotherapy and chemotherapy, and with immunosuppression. 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; 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 ... -
Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.
Clarke, M; Mackay, A; Ismer, B; Pickles, JC; Tatevossian, RG; et al. (AMER ASSOC CANCER RESEARCH, 2020-07-01)Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases ... -
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 ... -
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; et al. (PUBLIC LIBRARY SCIENCE, 2014-03-25)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 intracranial tumour growth patterns with multiparametric MRI incorporating Gd-DTPA and USPIO-enhanced imaging.
Boult, JKR; Borri, M; Jury, A; Popov, S; Box, G; et al. (WILEY, 2016-11-01)High grade and metastatic brain tumours exhibit considerable spatial variations in proliferation, angiogenesis, invasion, necrosis and oedema. Vascular heterogeneity arising from vascular co-option in regions of invasive ... -
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; et al. (AMER ASSOC CANCER RESEARCH, 2019-11-15)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 ... -
Metabolic biomarkers of response to the AKT inhibitor MK-2206 in pre-clinical models of human colorectal and prostate carcinoma.
Al-Saffar, NMS; Troy, H; Wong Te Fong, A-C; Paravati, R; Jackson, LE; et al. (NATURE PUBLISHING GROUP, 2018-10-30)BACKGROUND: AKT is commonly overexpressed in tumours and plays an important role in the metabolic reprogramming of cancer. We have used magnetic resonance spectroscopy (MRS) to assess whether inhibition of AKT signalling ... -
MRI Imaging of the Hemodynamic Vasculature of Neuroblastoma Predicts Response to Antiangiogenic Treatment.
Zormpas-Petridis, K; Jerome, NP; Blackledge, MD; Carceller, F; Poon, E; et al. (AMER ASSOC CANCER RESEARCH, 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 ... -
Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
Osborne, JD; Matthews, TP; McHardy, T; Proisy, N; Cheung, K-MJ; et al. (AMER CHEMICAL SOC, 2016-06-09)Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ... -
MYCN expression induces replication stress and sensitivity to PARP inhibition in neuroblastoma.
King, D; Li, XD; Almeida, GS; Kwok, C; Gravells, P; et al. (Impact Journals, LLC, 2020-06-09)This study investigates the influence expression of the MYCN oncogene has on the DNA damage response, replication fork progression and sensitivity to PARP inhibition in neuroblastoma. In a panel of neuroblastoma cell lines, ... -
Noninvasive MRI Native T1 Mapping Detects Response to MYCN-targeted Therapies in the Th-MYCN Model of Neuroblastoma.
Zormpas-Petridis, K; Poon, E; Clarke, M; Jerome, NP; Boult, JKR; et al. (AMER ASSOC CANCER RESEARCH, 2020-08-15)Noninvasive early indicators of treatment response are crucial to the successful delivery of precision medicine in children with cancer. Neuroblastoma is a common solid tumor of young children that arises from anomalies ... -
Orally bioavailable CDK9/2 inhibitor shows mechanism-based therapeutic potential in MYCN-driven neuroblastoma.
Poon, E; Liang, T; Jamin, Y; Walz, S; Kwok, C; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2020-11-02)The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show ...