Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development
Abstract The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populati...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Cell Communication and Signaling |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12964-023-01333-8 |
| _version_ | 1827770456723161088 |
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| author | Yifan Du Huimin Sun Zhiyuan Shi Xiuyuan Sui Bin Liu Zeyuan Zheng Yankuo Liu Zuodong Xuan Min Zhong Meiling Fu Yang Bai Qian Zhang Chen Shao |
| author_facet | Yifan Du Huimin Sun Zhiyuan Shi Xiuyuan Sui Bin Liu Zeyuan Zheng Yankuo Liu Zuodong Xuan Min Zhong Meiling Fu Yang Bai Qian Zhang Chen Shao |
| author_sort | Yifan Du |
| collection | DOAJ |
| description | Abstract The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment. Video Abstract |
| first_indexed | 2024-03-11T12:39:48Z |
| format | Article |
| id | doaj.art-99ac28747c40466fa538adaaddef39d1 |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-03-11T12:39:48Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell Communication and Signaling |
| spelling | doaj.art-99ac28747c40466fa538adaaddef39d12023-11-05T12:25:01ZengBMCCell Communication and Signaling1478-811X2023-11-0121111210.1186/s12964-023-01333-8Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer developmentYifan Du0Huimin Sun1Zhiyuan Shi2Xiuyuan Sui3Bin Liu4Zeyuan Zheng5Yankuo Liu6Zuodong Xuan7Min Zhong8Meiling Fu9Yang Bai10Qian Zhang11Chen Shao12Department of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityCentral Laboratory, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Endocrinology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityDepartment of Urology, Xiang’an Hospital of Xiamen University, School of Medicine, Xiamen UniversityAbstract The mutation of MET plays a crucial role in the initiation of cancer, while the Hedgehog (Hh) pathway also plays a significant role in cell differentiation and the maintenance of tumor stem cells. Conventional chemotherapy drugs are primarily designed to target the majority of cell populations within tumors rather than tumor stem cells. Consequently, after a brief period of remission, tumors often relapse. Moreover, the exclusive targeting of tumor stemness cell disregards the potential for other tumor cells to regain stemness and acquire drug resistance. As a result, current drugs that solely target the HGF/c-MET axis and the Hh pathway demonstrate only moderate efficacy in specific types of cancer. Mounting evidence indicates that these two pathways not only play important roles in cancer but also exert significant influence on the development of resistance to single-target therapies through the secretion of their own ligands. In this comprehensive review, we analyze and compare the potential impact of the Hh pathway on the tumor microenvironment (TME) in HGF/c-MET-driven tumor models, as well as the interplay between different cell types. Additionally, we further substantiate the potential and necessity of dual-pathway combination therapy as a critical target in MET addicted cancer treatment. Video Abstracthttps://doi.org/10.1186/s12964-023-01333-8MET mutationCancerHh pathwayCancer-associated fibroblasts (CAFs)HGF/c-MET axis |
| spellingShingle | Yifan Du Huimin Sun Zhiyuan Shi Xiuyuan Sui Bin Liu Zeyuan Zheng Yankuo Liu Zuodong Xuan Min Zhong Meiling Fu Yang Bai Qian Zhang Chen Shao Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development Cell Communication and Signaling MET mutation Cancer Hh pathway Cancer-associated fibroblasts (CAFs) HGF/c-MET axis |
| title | Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development |
| title_full | Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development |
| title_fullStr | Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development |
| title_full_unstemmed | Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development |
| title_short | Targeting the hedgehog pathway in MET mutation cancers and its effects on cells associated with cancer development |
| title_sort | targeting the hedgehog pathway in met mutation cancers and its effects on cells associated with cancer development |
| topic | MET mutation Cancer Hh pathway Cancer-associated fibroblasts (CAFs) HGF/c-MET axis |
| url | https://doi.org/10.1186/s12964-023-01333-8 |
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