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A subset of esophageal squamous cell carcinoma patient-derived xenografts respond to cetuximab, which is predicted by high EGFR expression and amplification

  
@article{JTD24191,
	author = {Hanting Zhu and Chunyu Wang and Jingjing Wang and Dawei Chen and Jiaying Deng and Jianyun Deng and Jianhong Fan and Harun Badakhshi and Xuesong Huang and Likun Zhang and Jie Cai and Sheng Guo and Wubin Qian and Yongzhan Nie and Qixiang Li and Kuaile Zhao},
	title = {A subset of esophageal squamous cell carcinoma patient-derived xenografts respond to cetuximab, which is predicted by high EGFR expression and amplification},
	journal = {Journal of Thoracic Disease},
	volume = {10},
	number = {9},
	year = {2018},
	keywords = {},
	abstract = {Background: Epidermal growth factor receptor (EGFR) is reportedly overexpressed in most esophageal tumors, but most targeted therapies showed no efficacy in non-selected patients. This study aims at investigating the adaptive cetuximab subset in a cohort of esophageal squamous cell carcinoma (ESCC) patient-derived xenografts (PDXs).
Methods: A large panel of ESCC PDXs has been established. The copy number, mRNA expression and immunohistochemistry (IHC) of key EGFR pathways have been examined along with cetuximab response. A preclinical trial on a randomly selected cohort of 16 ESCC PDXs was conducted, and the genomic annotations of these models were compared against the efficacy readout of the mouse trial.
Results: The trial identified that 7 of 16 (43.8%) responded to cetuximab (ΔT/ΔC <0 as responders). The gene amplification and expression analysis indicated that EGFR copy number ≥5 (P=0.035), high EGFR mRNA expression (P=0.001) and IHC score of 2–3 (P=0.034) are associated with tumor growth inhibition by cetuximab, suggesting EGFR may function as a single predictive biomarker for cetuximab response in ESCC.
Conclusions: Overall, our results suggest that an ESCC subtype with EGFR amplification and overexpression benefits from cetuximab treatment, which warrants further clinical confirmation.},
	issn = {2077-6624},	url = {http://jtd.amegroups.com/article/view/24191}
}