Drug repositioning for esophageal squamous cell carcinoma
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 E...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2022-09-01
|
| Series: | Frontiers in Genetics |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.991842/full |
| _version_ | 1811208230729154560 |
|---|---|
| author | Adam N. Bennett Rui Xuan Huang Qian He Nikki P. Lee Wing-Kin Sung Kei Hang Katie Chan Kei Hang Katie Chan Kei Hang Katie Chan |
| author_facet | Adam N. Bennett Rui Xuan Huang Qian He Nikki P. Lee Wing-Kin Sung Kei Hang Katie Chan Kei Hang Katie Chan Kei Hang Katie Chan |
| author_sort | Adam N. Bennett |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-12T04:18:29Z |
| format | Article |
| id | doaj.art-033db0cb18bf4e38bb33e0dcc6408dda |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-12T04:18:29Z |
| publishDate | 2022-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-033db0cb18bf4e38bb33e0dcc6408dda2022-12-22T03:48:20ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-09-011310.3389/fgene.2022.991842991842Drug repositioning for esophageal squamous cell carcinomaAdam N. Bennett0Rui Xuan Huang1Qian He2Nikki P. Lee3Wing-Kin Sung4Kei Hang Katie Chan5Kei Hang Katie Chan6Kei Hang Katie Chan7Jockey Club College of Veterinary Medicine and Life Sciences, City University of Hong Kong, Kowloon, Hong Kong SAR, ChinaDepartment of Electrical Engineering, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Surgery, The University of Hong Kong, Pokfulam, Hong Kong SAR, ChinaDepartment of Computer Sciences, National University of Singapore, Singapore, SingaporeDepartment of Electrical Engineering, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Biomedical Sciences, City University of Hong Kong, Hong Kong, Hong Kong SAR, ChinaDepartment of Epidemiology, Centre for Global Cardiometabolic Health, Brown University, Providence, RI, United StatesEsophageal 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.https://www.frontiersin.org/articles/10.3389/fgene.2022.991842/fulldrug repositioningdrug repurposingesophageal squamous cell carcinomaESCC treatmentcancer biology |
| spellingShingle | Adam N. Bennett Rui Xuan Huang Qian He Nikki P. Lee Wing-Kin Sung Kei Hang Katie Chan Kei Hang Katie Chan Kei Hang Katie Chan Drug repositioning for esophageal squamous cell carcinoma Frontiers in Genetics drug repositioning drug repurposing esophageal squamous cell carcinoma ESCC treatment cancer biology |
| title | Drug repositioning for esophageal squamous cell carcinoma |
| title_full | Drug repositioning for esophageal squamous cell carcinoma |
| title_fullStr | Drug repositioning for esophageal squamous cell carcinoma |
| title_full_unstemmed | Drug repositioning for esophageal squamous cell carcinoma |
| title_short | Drug repositioning for esophageal squamous cell carcinoma |
| title_sort | drug repositioning for esophageal squamous cell carcinoma |
| topic | drug repositioning drug repurposing esophageal squamous cell carcinoma ESCC treatment cancer biology |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.991842/full |
| work_keys_str_mv | AT adamnbennett drugrepositioningforesophagealsquamouscellcarcinoma AT ruixuanhuang drugrepositioningforesophagealsquamouscellcarcinoma AT qianhe drugrepositioningforesophagealsquamouscellcarcinoma AT nikkiplee drugrepositioningforesophagealsquamouscellcarcinoma AT wingkinsung drugrepositioningforesophagealsquamouscellcarcinoma AT keihangkatiechan drugrepositioningforesophagealsquamouscellcarcinoma AT keihangkatiechan drugrepositioningforesophagealsquamouscellcarcinoma AT keihangkatiechan drugrepositioningforesophagealsquamouscellcarcinoma |