Abstract
Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.
| Original language | English |
|---|---|
| Pages (from-to) | 6364-6374 |
| Number of pages | 11 |
| Journal | Cancer Research |
| Volume | 74 |
| Issue number | 21 |
| DOIs | |
| State | Published - Nov 1 2014 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma. / Wang, Zhiqiang; Da Silva, Thiago G.; Jin, Ke; Han, Xiaoqing; Ranganathan, Prathibha; Zhu, Xiaoxia; Sanchez-Mejias, Avencia; Bai, Feng; Li, Bin; Fei, Dennis Liang; Weaver, Kelly; Vasquez-Del Carpio, Rodrigo; Moscowitz, Anna E.; Koshenkov, Vadim P.; Sanchez, Lilly; Sparling, Lynne; Pei, Xin-Hai; Franceschi, Dido; Ribeiro, Afonso; Robbins, David J; Livingstone, Alan; Capobianco, Anthony J.
In: Cancer Research, Vol. 74, No. 21, 01.11.2014, p. 6364-6374.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma
AU - Wang, Zhiqiang
AU - Da Silva, Thiago G.
AU - Jin, Ke
AU - Han, Xiaoqing
AU - Ranganathan, Prathibha
AU - Zhu, Xiaoxia
AU - Sanchez-Mejias, Avencia
AU - Bai, Feng
AU - Li, Bin
AU - Fei, Dennis Liang
AU - Weaver, Kelly
AU - Vasquez-Del Carpio, Rodrigo
AU - Moscowitz, Anna E.
AU - Koshenkov, Vadim P.
AU - Sanchez, Lilly
AU - Sparling, Lynne
AU - Pei, Xin-Hai
AU - Franceschi, Dido
AU - Ribeiro, Afonso
AU - Robbins, David J
AU - Livingstone, Alan
AU - Capobianco, Anthony J
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.
AB - Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.
UR - http://www.scopus.com/inward/record.url?scp=84909609672&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84909609672&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-14-2051
DO - 10.1158/0008-5472.CAN-14-2051
M3 - Article
C2 - 25164006
AN - SCOPUS:84909609672
VL - 74
SP - 6364
EP - 6374
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0099-7013
IS - 21
ER -