The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma
In most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate transition in response to sorafenib or other targeted drugs in the presence or absence of genetic mutations. Therefore, understanding the...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2020-01-01
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| Series: | EBioMedicine |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396419308254 |
| _version_ | 1798044770104246272 |
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| author | Shunjie Xia Yu Pan Yuelong Liang Junjie Xu Xiujun Cai |
| author_facet | Shunjie Xia Yu Pan Yuelong Liang Junjie Xu Xiujun Cai |
| author_sort | Shunjie Xia |
| collection | DOAJ |
| description | In most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate transition in response to sorafenib or other targeted drugs in the presence or absence of genetic mutations. Therefore, understanding the major characteristics of drug-resistant cells state helps to discover new treatments that overcome drug resistance. To note, little is known about the metabolic or microenvironmental aspects of the certain tumor cell states beyond the genome. This review mainly focuses on the underlying mechanisms of acquired sorafenib resistance based on CSCs and EMT models, which explain tumor heterogeneity and have been considered the major cause of secondary sorafenib resistance. In particular, it discusses how the tumor microenvironment and tumor metabolism regulate cell stemness, mesenchymal state, and sorafenib resistance through epigenetic regulations, and provides reliable targets that might have synergetic effect with sorafenib. Keywords: Tumor metabolism, Tumor microenvironment, Hypoxia, Cancer stem cells, Epithelial-mesenchymal transition, Sorafenib resistance |
| first_indexed | 2024-04-11T23:09:36Z |
| format | Article |
| id | doaj.art-352b974e238848869f9417f76dca3a82 |
| institution | Directory Open Access Journal |
| issn | 2352-3964 |
| language | English |
| last_indexed | 2024-04-11T23:09:36Z |
| publishDate | 2020-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj.art-352b974e238848869f9417f76dca3a822022-12-22T03:57:53ZengElsevierEBioMedicine2352-39642020-01-0151The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinomaShunjie Xia0Yu Pan1Yuelong Liang2Junjie Xu3Xiujun Cai4Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaKey Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaCorresponding authors.; Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaCorresponding authors.; Key Laboratory of Laparoscopic Technology of Zhejiang Province, Department of General Surgery, Sir Run-Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou 310016, ChinaIn most cases, sorafenib-resistant HCC cells exhibit significant mesenchymal phenotype and stemness features. In this context, tumor cells might undergo cell fate transition in response to sorafenib or other targeted drugs in the presence or absence of genetic mutations. Therefore, understanding the major characteristics of drug-resistant cells state helps to discover new treatments that overcome drug resistance. To note, little is known about the metabolic or microenvironmental aspects of the certain tumor cell states beyond the genome. This review mainly focuses on the underlying mechanisms of acquired sorafenib resistance based on CSCs and EMT models, which explain tumor heterogeneity and have been considered the major cause of secondary sorafenib resistance. In particular, it discusses how the tumor microenvironment and tumor metabolism regulate cell stemness, mesenchymal state, and sorafenib resistance through epigenetic regulations, and provides reliable targets that might have synergetic effect with sorafenib. Keywords: Tumor metabolism, Tumor microenvironment, Hypoxia, Cancer stem cells, Epithelial-mesenchymal transition, Sorafenib resistancehttp://www.sciencedirect.com/science/article/pii/S2352396419308254 |
| spellingShingle | Shunjie Xia Yu Pan Yuelong Liang Junjie Xu Xiujun Cai The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma EBioMedicine |
| title | The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| title_full | The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| title_fullStr | The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| title_full_unstemmed | The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| title_short | The microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| title_sort | microenvironmental and metabolic aspects of sorafenib resistance in hepatocellular carcinoma |
| url | http://www.sciencedirect.com/science/article/pii/S2352396419308254 |
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