RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential
Abstract N6‐methyladenosine (m6A), the newest and most prevalent layer of internal epigenetic modification in eukaryotic mRNA, has been demonstrated to play a critical role in cancer biology. Increasing evidence has highlighted that the interaction between cancer stem cells (CSCs) and the tumor immu...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2021-09-01
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| Series: | Clinical and Translational Medicine |
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| Online Access: | https://doi.org/10.1002/ctm2.525 |
| _version_ | 1818740454436372480 |
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| author | Zhihui Zhang Chaoqi Zhang Yuejun Luo Guochao Zhang Peng Wu Nan Sun Jie He |
| author_facet | Zhihui Zhang Chaoqi Zhang Yuejun Luo Guochao Zhang Peng Wu Nan Sun Jie He |
| author_sort | Zhihui Zhang |
| collection | DOAJ |
| description | Abstract N6‐methyladenosine (m6A), the newest and most prevalent layer of internal epigenetic modification in eukaryotic mRNA, has been demonstrated to play a critical role in cancer biology. Increasing evidence has highlighted that the interaction between cancer stem cells (CSCs) and the tumor immune microenvironment (TIME) is the root cause of tumorigenesis, metastasis, therapy resistance, and recurrence. In recent studies, the m6A modification has been tightly linked to this CSC‐TIME interplay, participating in the regulation of CSCs and TIME remolding. Interestingly, the m6A modification has also been identified as a novel decisive factor in the efficacy of immunotherapies—particularly anti‐PD‐1/PD‐L1 monotherapies—by changing the plasticity of the TIME. Given the functional importance of the m6A modification in the crosstalk between CSCs and the TIME, targeting m6A regulators will open new avenues to overcome therapeutic resistance, especially for immune checkpoint‐based immunotherapy. In the present review, we summarize the current landscape of m6A modifications in CSCs and the TIME, and also prospect the underling role of m6A modifications at the crossroads of CSCs and the TIME for the first time. Additionally, to provide the possibility of modulating m6A modifications as an emerging therapeutic strategy, we also explore the burgeoning inhibitors and technologies targeting m6A regulators. Lastly, considering recent advances in m6A‐seq technologies and cancer drug development, we propose the future directions of m6A modification in clinical applications, which may not only help to improve individualized monitoring and therapy but also provide enhanced and durable responses in patients with insensitive tumors. |
| first_indexed | 2024-12-18T01:40:59Z |
| format | Article |
| id | doaj.art-449aeb55239243a3a8c2cc0f06836d94 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-12-18T01:40:59Z |
| publishDate | 2021-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-449aeb55239243a3a8c2cc0f06836d942022-12-21T21:25:19ZengWileyClinical and Translational Medicine2001-13262021-09-01119n/an/a10.1002/ctm2.525RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potentialZhihui Zhang0Chaoqi Zhang1Yuejun Luo2Guochao Zhang3Peng Wu4Nan Sun5Jie He6Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaDepartment of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing ChinaAbstract N6‐methyladenosine (m6A), the newest and most prevalent layer of internal epigenetic modification in eukaryotic mRNA, has been demonstrated to play a critical role in cancer biology. Increasing evidence has highlighted that the interaction between cancer stem cells (CSCs) and the tumor immune microenvironment (TIME) is the root cause of tumorigenesis, metastasis, therapy resistance, and recurrence. In recent studies, the m6A modification has been tightly linked to this CSC‐TIME interplay, participating in the regulation of CSCs and TIME remolding. Interestingly, the m6A modification has also been identified as a novel decisive factor in the efficacy of immunotherapies—particularly anti‐PD‐1/PD‐L1 monotherapies—by changing the plasticity of the TIME. Given the functional importance of the m6A modification in the crosstalk between CSCs and the TIME, targeting m6A regulators will open new avenues to overcome therapeutic resistance, especially for immune checkpoint‐based immunotherapy. In the present review, we summarize the current landscape of m6A modifications in CSCs and the TIME, and also prospect the underling role of m6A modifications at the crossroads of CSCs and the TIME for the first time. Additionally, to provide the possibility of modulating m6A modifications as an emerging therapeutic strategy, we also explore the burgeoning inhibitors and technologies targeting m6A regulators. Lastly, considering recent advances in m6A‐seq technologies and cancer drug development, we propose the future directions of m6A modification in clinical applications, which may not only help to improve individualized monitoring and therapy but also provide enhanced and durable responses in patients with insensitive tumors.https://doi.org/10.1002/ctm2.525cancer stem cellsimmune checkpointimmunotherapym6A modificationmetastasisrecurrence |
| spellingShingle | Zhihui Zhang Chaoqi Zhang Yuejun Luo Guochao Zhang Peng Wu Nan Sun Jie He RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential Clinical and Translational Medicine cancer stem cells immune checkpoint immunotherapy m6A modification metastasis recurrence |
| title | RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential |
| title_full | RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential |
| title_fullStr | RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential |
| title_full_unstemmed | RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential |
| title_short | RNA N6‐methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment: Current landscape and therapeutic potential |
| title_sort | rna n6 methyladenosine modification in the lethal teamwork of cancer stem cells and the tumor immune microenvironment current landscape and therapeutic potential |
| topic | cancer stem cells immune checkpoint immunotherapy m6A modification metastasis recurrence |
| url | https://doi.org/10.1002/ctm2.525 |
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