Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment
dc.contributor.author
dc.date.accessioned
2013-09-19T10:37:00Z
dc.date.available
2013-09-19T10:37:00Z
dc.date.issued
2012
dc.identifier.issn
1021-335X
dc.identifier.uri
dc.description.abstract
The recent identification of HER2 gene amplification as a novel predictor of resistance to the EGFR (HER2)-targeted antibody cetuximab and of response to combination therapies against EGFR and HER2 in wild-type KRAS tumor settings may represent a further step toward personalized medicine for patients with colorectal cancer. Herein, we show that transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification is a molecular phenomenon that takes place in EGFR-dependent, wild-type KRAS squamous cell carcinoma (SCC) cells that acquire resistance to cetuximab. Since cetuximab activity against cetuximab-refractory SCC cells can be fully restored in the presence of the anti-HER2 monoclonal antibody trastuzumab, our findings suggest that, beyond HER2 gene amplification, we might need to redefine the threshold values for HER2 positivity to improve the accuracy of the selection of cetuximab-refractory patients with wild-type KRAS that may benefit from receiving a cetuximab/trastuzumab combination
dc.format.mimetype
application/pdf
dc.language.iso
eng
dc.publisher
Spandidos Publications
dc.relation.isformatof
Reproducció digital del document publicat a: http://www.spandidos-publications.com/or/27/6/1887
dc.relation.ispartof
© Oncology Reports, 2012, vol. 27, núm. 6, p. 1887-1892
dc.relation.ispartofseries
Articles publicats (D-B)
dc.rights
Tots els drets reservats
dc.subject
dc.title
Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment
dc.type
info:eu-repo/semantics/article
dc.rights.accessRights
info:eu-repo/semantics/openAccess
dc.embargo.terms
Cap
dc.type.version
info:eu-repo/semantics/publishedVersion
dc.identifier.doi
dc.identifier.idgrec
018316
dc.identifier.eissn
1791-2431