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dc.contributor.authorZormpas-Petridis, K
dc.contributor.authorPoon, E
dc.contributor.authorClarke, M
dc.contributor.authorJerome, NP
dc.contributor.authorBoult, JKR
dc.contributor.authorBlackledge, MD
dc.contributor.authorCarceller, F
dc.contributor.authorKoers, A
dc.contributor.authorBarone, G
dc.contributor.authorPearson, ADJ
dc.contributor.authorMoreno, L
dc.contributor.authorAnderson, J
dc.contributor.authorSebire, N
dc.contributor.authorMcHugh, K
dc.contributor.authorKoh, D-M
dc.contributor.authorChesler, L
dc.contributor.authorYuan, Y
dc.contributor.authorRobinson, SP
dc.contributor.authorJamin, Y
dc.date.accessioned2020-06-15T08:37:44Z
dc.date.issued2020-08
dc.identifier.citationCancer research, 2020, 80 (16), pp. 3424 - 3435
dc.identifier.issn0008-5472
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3731
dc.identifier.eissn1538-7445
dc.identifier.doi10.1158/0008-5472.can-20-0133
dc.description.abstractNoninvasive 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 in neural crest development. Therapeutic approaches aiming to destabilize MYCN protein, such as small-molecule inhibitors of Aurora A and mTOR, are currently being evaluated in early phase clinical trials in children with high-risk MYCN -driven disease, with limited ability to evaluate conventional pharmacodynamic biomarkers of response. T 1 mapping is an MRI scan that measures the proton spin-lattice relaxation time T 1 . Using a multiparametric MRI-pathologic cross-correlative approach and computational pathology methodologies including a machine learning-based algorithm for the automatic detection and classification of neuroblasts, we show here that T 1 mapping is sensitive to the rich histopathologic heterogeneity of neuroblastoma in the Th- MYCN transgenic model. Regions with high native T 1 corresponded to regions dense in proliferative undifferentiated neuroblasts, whereas regions characterized by low T 1 were rich in apoptotic or differentiating neuroblasts. Reductions in tumor-native T 1 represented a sensitive biomarker of response to treatment-induced apoptosis with two MYCN -targeted small-molecule inhibitors, Aurora A kinase inhibitor alisertib (MLN8237) and mTOR inhibitor vistusertib (AZD2014). Overall, we demonstrate the potential of T 1 mapping, a scan readily available on most clinical MRI scanners, to assess response to therapy and guide clinical trials for children with neuroblastoma. The study reinforces the potential role of MRI-based functional imaging in delivering precision medicine to children with neuroblastoma. SIGNIFICANCE: This study shows that MRI-based functional imaging can detect apoptotic responses to MYCN -targeted small-molecule inhibitors in a genetically engineered murine model of MYCN -driven neuroblastoma.
dc.formatPrint-Electronic
dc.format.extent3424 - 3435
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectAnimals
dc.subjectMice, Transgenic
dc.subjectHumans
dc.subjectMice
dc.subjectNeuroblastoma
dc.subjectBenzamides
dc.subjectAzepines
dc.subjectMorpholines
dc.subjectPyrimidines
dc.subjectProtein Kinase Inhibitors
dc.subjectTreatment Outcome
dc.subjectAlgorithms
dc.subjectTime Factors
dc.subjectChild
dc.subjectFemale
dc.subjectMale
dc.subjectTOR Serine-Threonine Kinases
dc.subjectMachine Learning
dc.subjectPrecision Medicine
dc.subjectN-Myc Proto-Oncogene Protein
dc.subjectMultiparametric Magnetic Resonance Imaging
dc.titleNoninvasive MRI Native T<sub>1</sub> Mapping Detects Response to <i>MYCN</i>-targeted Therapies in the Th-<i>MYCN</i> Model of Neuroblastoma.
dc.typeJournal Article
dcterms.dateAccepted2020-06-11
rioxxterms.versionofrecord10.1158/0008-5472.can-20-0133
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2020-08
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer research
pubs.issue16
pubs.notesNot known
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Computational Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Computational Pathology & Integrated Genomics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Paediatric Solid Tumour Biology and Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Computational Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Pre-Clinical MRI
pubs.organisational-group/ICR/Primary Group/Royal Marsden Clinical Units
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/16/17 Starting Cohort
pubs.publication-statusPublished
pubs.volume80
pubs.embargo.termsNot known
icr.researchteamComputational Pathology & Integrated Genomicsen_US
icr.researchteamPaediatric Solid Tumour Biology and Therapeuticsen_US
icr.researchteamComputational Imagingen_US
icr.researchteamPre-Clinical MRIen_US
dc.contributor.icrauthorZormpas Petridis, Konstantinosen
dc.contributor.icrauthorKoh, Dow-Muen
dc.contributor.icrauthorJamin, Yannen
dc.contributor.icrauthorPoon, Evonen
dc.contributor.icrauthorRobinson, Simonen
dc.contributor.icrauthorBoult, Jessicaen
dc.contributor.icrauthorChesler, Louisen
dc.contributor.icrauthorYuan, Yinyinen
dc.contributor.icrauthorBlackledge, Matthewen


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