dc.contributor.author | Zormpas-Petridis, K | |
dc.contributor.author | Poon, E | |
dc.contributor.author | Clarke, M | |
dc.contributor.author | Jerome, NP | |
dc.contributor.author | Boult, JKR | |
dc.contributor.author | Blackledge, MD | |
dc.contributor.author | Carceller, F | |
dc.contributor.author | Koers, A | |
dc.contributor.author | Barone, G | |
dc.contributor.author | Pearson, ADJ | |
dc.contributor.author | Moreno, L | |
dc.contributor.author | Anderson, J | |
dc.contributor.author | Sebire, N | |
dc.contributor.author | McHugh, K | |
dc.contributor.author | Koh, D-M | |
dc.contributor.author | Chesler, L | |
dc.contributor.author | Yuan, Y | |
dc.contributor.author | Robinson, SP | |
dc.contributor.author | Jamin, Y | |
dc.date.accessioned | 2020-06-15T08:37:44Z | |
dc.date.issued | 2020-08 | |
dc.identifier.citation | Cancer research, 2020, 80 (16), pp. 3424 - 3435 | |
dc.identifier.issn | 0008-5472 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3731 | |
dc.identifier.eissn | 1538-7445 | |
dc.identifier.doi | 10.1158/0008-5472.can-20-0133 | |
dc.description.abstract | 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 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.format | Print-Electronic | |
dc.format.extent | 3424 - 3435 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Animals | |
dc.subject | Mice, Transgenic | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Neuroblastoma | |
dc.subject | Benzamides | |
dc.subject | Azepines | |
dc.subject | Morpholines | |
dc.subject | Pyrimidines | |
dc.subject | Protein Kinase Inhibitors | |
dc.subject | Treatment Outcome | |
dc.subject | Algorithms | |
dc.subject | Time Factors | |
dc.subject | Child | |
dc.subject | Female | |
dc.subject | Male | |
dc.subject | TOR Serine-Threonine Kinases | |
dc.subject | Machine Learning | |
dc.subject | Precision Medicine | |
dc.subject | N-Myc Proto-Oncogene Protein | |
dc.subject | Multiparametric Magnetic Resonance Imaging | |
dc.title | Noninvasive 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.type | Journal Article | |
dcterms.dateAccepted | 2020-06-11 | |
rioxxterms.versionofrecord | 10.1158/0008-5472.can-20-0133 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-08 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Cancer research | |
pubs.issue | 16 | |
pubs.notes | Not 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-status | Published | |
pubs.volume | 80 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Computational Pathology & Integrated Genomics | en_US |
icr.researchteam | Paediatric Solid Tumour Biology and Therapeutics | en_US |
icr.researchteam | Computational Imaging | en_US |
icr.researchteam | Pre-Clinical MRI | en_US |
dc.contributor.icrauthor | Zormpas Petridis, Konstantinos | en |
dc.contributor.icrauthor | Koh, Dow-Mu | en |
dc.contributor.icrauthor | Jamin, Yann | en |
dc.contributor.icrauthor | Poon, Evon | en |
dc.contributor.icrauthor | Robinson, Simon | en |
dc.contributor.icrauthor | Boult, Jessica | en |
dc.contributor.icrauthor | Chesler, Louis | en |
dc.contributor.icrauthor | Yuan, Yinyin | en |
dc.contributor.icrauthor | Blackledge, Matthew | en |