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Esophageal cancer (EC) remains a significant challenge globally, having the 8th highest incidence and 6th highest mortality worldwide. Esophageal squamous cell carcinoma (ESCC) is the most common form of EC in Asia. Crucially, more than 90% of EC cases in China are ESCC. The high mortality rate of EC is likely due to the limited number of effective therapeutic options. To increase patient survival, novel therapeutic strategies for EC patients must be devised. Unfortunately, the development of novel drugs also presents its own significant challenges as most novel drugs do not make it to market due to lack of efficacy or safety concerns. A more time and cost-effective strategy is to identify existing drugs, that have already been approved for treatment of other diseases, which can be repurposed to treat EC patients, with drug repositioning. This can be achieved by comparing the gene expression profiles of disease-states with the effect on gene-expression by a given drug. In our analysis, we used previously published microarray data and identified 167 differentially expressed genes (DEGs). Using weighted key driver analysis, 39 key driver genes were then identified. These driver genes were then used in Overlap Analysis and Network Analysis in Pharmomics. By extracting drugs common to both analyses, 24 drugs are predicted to demonstrate therapeutic effect in EC patients. Several of which have already been shown to demonstrate a therapeutic effect in EC, most notably Doxorubicin, which is commonly used to treat EC patients, and Ixazomib, which was recently shown to induce apoptosis and supress growth of EC cell lines. Additionally, our analysis predicts multiple psychiatric drugs, including Venlafaxine, as repositioned drugs. This is in line with recent research which suggests that psychiatric drugs should be investigated for use in gastrointestinal cancers such as EC. Our study shows that a drug repositioning approach is a feasible strategy for identifying novel ESCC therapies and can also improve the understanding of the mechanisms underlying the drug targets. [ABSTRACT FROM AUTHOR]

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer and the leading cause of cancer-related mortality worldwide, especially in Asia. In this study, the gene CKAP2L was selected by GEO, TCGA, and GTEx database analysis. The high expression of CKAP2L is related to the occurrence and development of ESCC. In addition, CKAP2L knockdown can inhibit the growth and migration of ESCC cells, while CKAP2L overexpression has the opposite effect. Furthermore, in vivo experiments indicated that down-regulation of CKAP2L can inhibit the tumorigenesis of ESCC cells. KEGG pathway analysis and the STRING database explored the relationship between cell cycle and CKAP2L and verified that depletion of CKAP2L markedly arrested cell cycle in the G2/M phase. Meanwhile, CKAP2L knockdown increased the sensitivity of ESCC cells to flavopiridol, the first CDK inhibitor to be tested in clinical trials, leading to an observable reduction in cell proliferation and an increase in cellular apoptosis. In brief, we identified CKAP2L as a tumor promoter, potential prognostic indicator, and therapeutic target of ESCC, which may play a role in regulating cell cycle progression. [ABSTRACT FROM AUTHOR]

Background: Esophageal Squamous Cell Carcinoma (ESCC) is a major subtype of esophageal cancer causing significant morbility and mortality in Asia. Mechanism of initiation and progression of this disease is unclear. Tumor initiating cells (TICs) are the subpopulation of cells which have the ability to self-renew, as well as, to drive initiation and progression of cancer. Increasing evidence has shown that TICs exist in a variety of tumors. However, the identification and characterization of TICs in esophageal carcinoma has remained elusive. Methodology/Principal Findings: to identify TICs in ESCC, ESCC cell lines including two primary cells were used for screening suitable surface marker. Then colony formation assay, drug resistant assay and tumorigenicity assay in immune deficient mice were used to characterize TICs in ESCC. We found that just the CD44 expression correlated with tumorigenicity in ESCC cell lines. And then induced differentiation of ESCC cells by all-trans retinoic acid treatment led to decreased expression of CD44. The FACS isolated cell subpopulations with high CD44 expression showed increased colony formation and drug resistance in vitro, as well as significantly enhanced tumorigenicity in NOD/SICD mice, as compared to the low expressing CD44 ESCC cells. Conclusions/Significance: our study has discovered a novel TIC surface marker, CD44, which can be utilized to enrich efficiently the TICs in ESCC. These findings will be useful for further studies of these cells and exploring therapeutic approaches. [ABSTRACT FROM AUTHOR]