Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma
Esophageal squamous cell carcinoma (ESCC) is strongly characterized by a male predominance with higher mortality rates and worse responses to treatment in males versus females. Despite the role of sex hormones, other causes that may contribute to sex bias in ESCC remain largely unknown, especially a...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/23/5854 |
| _version_ | 1797463520007159808 |
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| author | Yin Yin Xiao Yu Riyue Feng Yang Li Yahui Zhao Zhihua Liu |
| author_facet | Yin Yin Xiao Yu Riyue Feng Yang Li Yahui Zhao Zhihua Liu |
| author_sort | Yin Yin |
| collection | DOAJ |
| description | Esophageal squamous cell carcinoma (ESCC) is strongly characterized by a male predominance with higher mortality rates and worse responses to treatment in males versus females. Despite the role of sex hormones, other causes that may contribute to sex bias in ESCC remain largely unknown, especially as age increases and the hormone difference begins to diminish between sexes. In this study, we analyzed genomics, transcriptomics, and epigenomics from 663 ESCC patients and found that G2/M checkpoint pathway-related sex bias and age bias were significantly present in multi-omics data. In accordance with gene expression patterns across sexes, ten compounds were identified by applying drug repurposing from three drug sensitivity databases: The Connective Map (CMap), Genomics of Drug Sensitivity in Cancer (GDSC), and The Cancer Therapeutic Response Portal (CTRP). MK1775 and decitabine showed better efficacy in two male ESCC cell lines in vitro and in vivo. The drugs’ relevance to the transition between G2 and M was especially evident in male cell lines. In our study, we first validated the sex bias of the G2/M checkpoint pathway in ESCC and then determined that G2/M targets may be included in combination therapy for male patients to improve the efficacy of ESCC treatment. |
| first_indexed | 2024-03-09T17:52:52Z |
| format | Article |
| id | doaj.art-f90bfcf0ef0b4511a9a3f933a118ee8d |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T17:52:52Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-f90bfcf0ef0b4511a9a3f933a118ee8d2023-11-24T10:39:46ZengMDPI AGCancers2072-66942022-11-011423585410.3390/cancers14235854Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell CarcinomaYin Yin0Xiao Yu1Riyue Feng2Yang Li3Yahui Zhao4Zhihua Liu5State Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaState Key Laboratory of Molecular Oncology, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, ChinaEsophageal squamous cell carcinoma (ESCC) is strongly characterized by a male predominance with higher mortality rates and worse responses to treatment in males versus females. Despite the role of sex hormones, other causes that may contribute to sex bias in ESCC remain largely unknown, especially as age increases and the hormone difference begins to diminish between sexes. In this study, we analyzed genomics, transcriptomics, and epigenomics from 663 ESCC patients and found that G2/M checkpoint pathway-related sex bias and age bias were significantly present in multi-omics data. In accordance with gene expression patterns across sexes, ten compounds were identified by applying drug repurposing from three drug sensitivity databases: The Connective Map (CMap), Genomics of Drug Sensitivity in Cancer (GDSC), and The Cancer Therapeutic Response Portal (CTRP). MK1775 and decitabine showed better efficacy in two male ESCC cell lines in vitro and in vivo. The drugs’ relevance to the transition between G2 and M was especially evident in male cell lines. In our study, we first validated the sex bias of the G2/M checkpoint pathway in ESCC and then determined that G2/M targets may be included in combination therapy for male patients to improve the efficacy of ESCC treatment.https://www.mdpi.com/2072-6694/14/23/5854esophageal squamous cell carcinomasex biasagingG2/M checkpointdrug repurposing |
| spellingShingle | Yin Yin Xiao Yu Riyue Feng Yang Li Yahui Zhao Zhihua Liu Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma Cancers esophageal squamous cell carcinoma sex bias aging G2/M checkpoint drug repurposing |
| title | Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma |
| title_full | Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma |
| title_fullStr | Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma |
| title_full_unstemmed | Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma |
| title_short | Drug Repurposing Applications to Overcome Male Predominance via Targeting G2/M Checkpoint in Human Esophageal Squamous Cell Carcinoma |
| title_sort | drug repurposing applications to overcome male predominance via targeting g2 m checkpoint in human esophageal squamous cell carcinoma |
| topic | esophageal squamous cell carcinoma sex bias aging G2/M checkpoint drug repurposing |
| url | https://www.mdpi.com/2072-6694/14/23/5854 |
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