PMID- 28881608
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20170925
LR  - 20181113
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 31
DP  - 2017 Aug 1
TI  - Anti-tumor efficacy of theliatinib in esophageal cancer patient-derived 
      xenografts models with epidermal growth factor receptor (EGFR) overexpression and 
      gene amplification.
PG  - 50832-50844
LID - 10.18632/oncotarget.17243 [doi]
AB  - Targeted therapy is not yet approved for esophageal cancer (EC). In this study, 
      we first evaluated EGFR gene and protein expression in 70 Chinese EC patient 
      tumor samples collected during surgery. We then established 23 patient-derived EC 
      xenograft (PDECX) models and assessed the efficacy of theliatinib, a potent and 
      highly selective EGFR inhibitor currently in Phase I clinical study, in 9 PDECX 
      models exhibiting various EGFR expression levels. Immunohistochemical analysis 
      showed that 50 patient tumor samples (71.4%) had high EGFR expression. 
      Quantitative PCR showed that eight tumors (11.6%) had EGFR gene copy number gain, 
      and fluorescence in situ hybridization (FISH) revealed that four tumors had EGFR 
      gene amplification. These results suggest that EGFR protein may be overexpressed 
      in many EC tumors without gene amplification. Also detected were rare hot-spot 
      mutations in EGFR and PIK3CA, whereas no mutations were found in K-Ras or B-Raf. 
      Theliatinib exhibited strong antitumor activity in PDECX models with high EGFR 
      expression, including remarkable tumor regression in two PDECX models with both 
      EGFR gene amplification and protein overexpression. However, the efficacy of 
      theliatinib was diminished in models with PI3KCA mutations or FGFR1 
      overexpression in addition to high EGFR expression. This study demonstrates that 
      theliatinib could potentially benefit EC patients with high EGFR protein 
      expression without mutations or aberrant activities of associated factors, such 
      as PI3KCA or FGFR1.
FAU - Ren, Yongxin
AU  - Ren Y
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Zheng, Jianming
AU  - Zheng J
AD  - Department of Pathology, Changhai Hospital, the Second Military Medical 
      University, Shanghai, China.
FAU - Fan, Shiming
AU  - Fan S
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Wang, Linfang
AU  - Wang L
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Cheng, Min
AU  - Cheng M
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Shi, Dongxia
AU  - Shi D
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Zhang, Wei
AU  - Zhang W
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Tang, Renxiang
AU  - Tang R
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Yu, Ying
AU  - Yu Y
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Jiao, Longxian
AU  - Jiao L
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Ni, Jun
AU  - Ni J
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Yang, Haibin
AU  - Yang H
AD  - Department of Chemistry, Hutchison MediPharma Limited, Shanghai, China.
FAU - Cai, Huaqing
AU  - Cai H
AD  - Department of Chemistry, Hutchison MediPharma Limited, Shanghai, China.
FAU - Yin, Fang
AU  - Yin F
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Chen, Yunxin
AU  - Chen Y
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Zhou, Feng
AU  - Zhou F
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Zhang, Weihan
AU  - Zhang W
AD  - Department of Chemistry, Hutchison MediPharma Limited, Shanghai, China.
FAU - Qing, Weiguo
AU  - Qing W
AD  - Department of Oncology Research, Hutchison MediPharma Limited, Shanghai, China.
FAU - Su, Weiguo
AU  - Su W
AD  - Department of Chemistry, Hutchison MediPharma Limited, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20170419
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5584209
OTO - NOTNLM
OT  - EGFR targeted therapy
OT  - esophageal cancer
OT  - patient derived xenograft models
OT  - theliatinib
COIS- CONFLICTS OF INTEREST All authors disclose no conflicts of interest.
EDAT- 2017/09/09 06:00
MHDA- 2017/09/09 06:01
PMCR- 2017/08/01
CRDT- 2017/09/09 06:00
PHST- 2016/12/01 00:00 [received]
PHST- 2017/03/27 00:00 [accepted]
PHST- 2017/09/09 06:00 [entrez]
PHST- 2017/09/09 06:00 [pubmed]
PHST- 2017/09/09 06:01 [medline]
PHST- 2017/08/01 00:00 [pmc-release]
AID - 17243 [pii]
AID - 10.18632/oncotarget.17243 [doi]
PST - epublish
SO  - Oncotarget. 2017 Apr 19;8(31):50832-50844. doi: 10.18632/oncotarget.17243. 
      eCollection 2017 Aug 1.