dc.contributor.author | Martins, CD | |
dc.contributor.author | Da Pieve, C | |
dc.contributor.author | Burley, TA | |
dc.contributor.author | Smith, R | |
dc.contributor.author | Ciobota, DM | |
dc.contributor.author | Allott, L | |
dc.contributor.author | Harrington, KJ | |
dc.contributor.author | Oyen, WJG | |
dc.contributor.author | Smith, G | |
dc.contributor.author | Kramer-Marek, G | |
dc.date.accessioned | 2018-04-20T09:34:53Z | |
dc.date.issued | 2018-04-15 | |
dc.identifier.citation | Clinical cancer research : an official journal of the American Association for Cancer Research, 2018, 24 (8), pp. 1853 - 1865 | |
dc.identifier.issn | 1078-0432 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/1649 | |
dc.identifier.eissn | 1557-3265 | |
dc.identifier.doi | 10.1158/1078-0432.ccr-17-2754 | |
dc.description.abstract | Purpose: Recent studies have highlighted a role of HER3 in HER2-driven cancers (e.g., breast cancer), implicating the upregulation of the receptor in resistance to HER-targeted therapies and Hsp90 inhibitors (e.g., AUY922). Therefore, we have developed an affibody-based PET radioconjugate that quantitatively assesses HER3 changes induced by Hsp90 inhibition in vivoExperimental Design: ZHER3:8698 affibody molecules were conjugated via the C-terminus cysteine to DFO-maleimide for 89Zr radiolabeling. The probe was characterized in vitro and in vivo in a panel of human breast cell lines and xenograft models with varying HER3 receptor levels. In addition, the radioconjugate was investigated as a tool to monitor the outcome of AUY922, an Hsp90 inhibitor, in an MCF-7 xenograft model.Results: We demonstrated that 89Zr-DFO-ZHER3:8698 can track changes in receptor expression in HER3-positive xenograft models and monitor the outcome of AUY922 treatment. Our in vitro findings showed that MCF-7 cells, which are phenotypically different from BT474, develop resistance to treatment with AUY922 through HER3/IGF-1Rβ-mediated signaling. Of note, the lack of response in vitro due to HER3 recovery was confirmed in vivo using 89Zr-DFO-ZHER3:8698-based imaging. Upon AUY922 treatment, higher radioconjugate uptake was detected in treated MCF-7 xenografts, correlating with an AUY922-induced HER3 upregulation concomitant with an increase in IGF-1Rβ expression.Conclusions: These data underline the potential of HER3-based PET imaging to noninvasively provide information about HER3 expression and to identify patients not responding to targeted therapies due to HER3 recovery. Clin Cancer Res; 24(8); 1853-65. ©2018 AACR. | |
dc.format | Print-Electronic | |
dc.format.extent | 1853 - 1865 | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | AMER ASSOC CANCER RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Cell Line, Tumor | |
dc.subject | Animals | |
dc.subject | Humans | |
dc.subject | Mice | |
dc.subject | Breast Neoplasms | |
dc.subject | Disease Models, Animal | |
dc.subject | Resorcinols | |
dc.subject | Isoxazoles | |
dc.subject | Receptor, erbB-3 | |
dc.subject | Immunoconjugates | |
dc.subject | Radiopharmaceuticals | |
dc.subject | Positron-Emission Tomography | |
dc.subject | Radiography | |
dc.subject | Gene Expression Profiling | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Female | |
dc.subject | HSP90 Heat-Shock Proteins | |
dc.subject | Heterografts | |
dc.subject | Biomarkers, Tumor | |
dc.title | HER3-Mediated Resistance to Hsp90 Inhibition Detected in Breast Cancer Xenografts by Affibody-Based PET Imaging. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-02-01 | |
rioxxterms.versionofrecord | 10.1158/1078-0432.ccr-17-2754 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-04 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Clinical cancer research : an official journal of the American Association for Cancer Research | |
pubs.issue | 8 | |
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 Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/PET Radiochemistry | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Molecular Imaging | |
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 Biology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Closed research teams/PET Radiochemistry | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Preclinical Molecular Imaging | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Translational Molecular Imaging | |
pubs.publication-status | Published | |
pubs.volume | 24 | |
pubs.embargo.terms | Not known | |
icr.researchteam | PET Radiochemistry | |
icr.researchteam | Preclinical Molecular Imaging | |
icr.researchteam | Targeted Therapy | |
icr.researchteam | Translational Molecular Imaging | |
dc.contributor.icrauthor | Da Pieve, Chiara | |
dc.contributor.icrauthor | Harrington, Kevin | |
dc.contributor.icrauthor | Smith, Graham | |
dc.contributor.icrauthor | Kramer-Marek, Gabriela | |