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Title:	Transcriptional upregulation of HER2 expression in the absence of HER2 gene amplification results in cetuximab resistance that is reversed by trastuzumab treatment
Author:	Oliveras Ferrarós, Cristina; Massaguer i Vall-llovera, Anna; Vázquez Martín, Alejandro; Carrion Salip, Dolors; Queralt, Bernardo; Cufí González, Sílvia; Martin Castillo, Begoña; Bosch Barrera, Joaquim; Brunet i Vidal, Joan; Llorens Duran, Rafael de; Menéndez Menéndez, Javier Abel
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
Subject(s):	-Càncer -- Tractament -Cancer -- Treatment -Recte -- Càncer -Rectum -- Cancer -Medicaments antineoplàstics -Antineoplastic agents
Rights:	Tots els drets reservats
Document type:	Article Article - Published version
Published by:	Spandidos Publications
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