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Oncotarget. 2018 Jan 1;9(26):18422-18434. doi: 10.18632/oncotarget.24853. eCollection 2018 Apr 6.

Identification of spleen tyrosine kinase as a potential therapeutic target for esophageal squamous cell carcinoma using reverse phase protein arrays.

Author information

1
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
2
Sidney Kimmel Comprehensive Cancer Centre, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
3
School of Life and Allied Health Sciences, Glocal University, Saharanpur, India.
4
Institute of Bioinformatics, International Technology Park, Bangalore, India.
5
Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Kollam, India.
6
Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India.
7
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
8
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
9
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
10
Manipal Academy of Higher Education (MAHE), Manipal, India.

Abstract

The vast majority of esophageal cancers in China, India and Iran are esophageal squamous cell carcinomas (ESCC). A timely diagnosis provides surgical removal as the main therapeutic option for patients with ESCC. Currently, there are no targeted therapies available for ESCC. We carried out reverse phase protein array-based protein expression profiling of seven ESCC-derivedcell lines and a non-neoplastic esophageal epithelial cell line (Het-1A) to identify differentially expressed proteins in ESCC. SYK non-receptortyrosine kinase was overexpressed in six out of seven ESCC cell lines that were used in the study. We evaluated the role of SYK in ESCC using the pharmacological inhibitor entospletinib (GS-9973) and siRNA-based knock down studies. Entospletinib is a selective inhibitor of SYK, which is currently being evaluated in phase II clinical trials for hematological malignancies. Using in vivo subcutaneous tumor xenografts in mice, we demonstrate that treatment with entospletinib significantly inhibits tumor growth. Further clinical studies are needed to prove the efficacy of entospletinib as a targeted therapeutic agent for treating ESCC.

KEYWORDS:

ESCC; RPPA; SYK; entospletinib

Conflict of interest statement

CONFLICTS OF INTEREST The authors declare no conflicts of interest.

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