Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH
Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treat...
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MDPI AG
2021-08-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/9/2250 |
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| author | Sunil Kumar Parth Sarthi Indra Mani Muhammad Umer Ashraf Myeong-Ho Kang Vishal Kumar Yong-Soo Bae |
| author_facet | Sunil Kumar Parth Sarthi Indra Mani Muhammad Umer Ashraf Myeong-Ho Kang Vishal Kumar Yong-Soo Bae |
| author_sort | Sunil Kumar |
| collection | DOAJ |
| description | Cellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, some cancer patients escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required urgently. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidence, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N<sup>6</sup>A-modification machineries which can be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover, and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signaling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine. |
| first_indexed | 2024-03-10T07:49:09Z |
| format | Article |
| id | doaj.art-3a86580c1051408fb7a0086a7285887b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T07:49:09Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3a86580c1051408fb7a0086a7285887b2023-11-22T12:23:11ZengMDPI AGCells2073-44092021-08-01109225010.3390/cells10092250Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISHSunil Kumar0Parth Sarthi1Indra Mani2Muhammad Umer Ashraf3Myeong-Ho Kang4Vishal Kumar5Yong-Soo Bae6Department of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, KoreaUniversity Department of Botany, M.Sc. Biotechnology, Ranchi University, Ranchi 834008, IndiaDepartment of Microbiology, Gargi College, University of Delhi, New Delhi 110049, IndiaDepartment of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, KoreaDepartment of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, KoreaDepartment of Pharmaceutical Science, Dayananda Sagar University, Bengaluru 560078, IndiaDepartment of Biological Sciences, Sungkyunkwan University, Jangan-gu, Suwon 16419, Gyeonggi-do, KoreaCellular immunotherapy has recently emerged as a fourth pillar in cancer treatment co-joining surgery, chemotherapy and radiotherapy. Where, the discovery of immune checkpoint blockage or inhibition (ICB/ICI), anti-PD-1/PD-L1 and anti-CTLA4-based, therapy has revolutionized the class of cancer treatment at a different level. However, some cancer patients escape this immune surveillance mechanism and become resistant to ICB-therapy. Therefore, a more advanced or an alternative treatment is required urgently. Despite the functional importance of epitranscriptomics in diverse clinico-biological practices, its role in improving the efficacy of ICB therapeutics has been limited. Consequently, our study encapsulates the evidence, as a possible strategy, to improve the efficacy of ICB-therapy by co-targeting molecular checkpoints especially N<sup>6</sup>A-modification machineries which can be reformed into RNA modifying drugs (RMD). Here, we have explained the mechanism of individual RNA-modifiers (editor/writer, eraser/remover, and effector/reader) in overcoming the issues associated with high-dose antibody toxicities and drug-resistance. Moreover, we have shed light on the importance of suppressor of cytokine signaling (SOCS/CISH) and microRNAs in improving the efficacy of ICB-therapy, with brief insight on the current monoclonal antibodies undergoing clinical trials or already approved against several solid tumor and metastatic cancers. We anticipate our investigation will encourage researchers and clinicians to further strengthen the efficacy of ICB-therapeutics by considering the importance of epitranscriptomics as a personalized medicine.https://www.mdpi.com/2073-4409/10/9/2250epitranscriptomicsimmune checkpoint blockage (ICB) therapyanti-PD-1/PD-L1 drug resistancepersonalized medicineCISHmicroRNAs |
| spellingShingle | Sunil Kumar Parth Sarthi Indra Mani Muhammad Umer Ashraf Myeong-Ho Kang Vishal Kumar Yong-Soo Bae Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH Cells epitranscriptomics immune checkpoint blockage (ICB) therapy anti-PD-1/PD-L1 drug resistance personalized medicine CISH microRNAs |
| title | Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH |
| title_full | Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH |
| title_fullStr | Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH |
| title_full_unstemmed | Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH |
| title_short | Epitranscriptomic Approach: To Improve the Efficacy of ICB Therapy by Co-Targeting Intracellular Checkpoint CISH |
| title_sort | epitranscriptomic approach to improve the efficacy of icb therapy by co targeting intracellular checkpoint cish |
| topic | epitranscriptomics immune checkpoint blockage (ICB) therapy anti-PD-1/PD-L1 drug resistance personalized medicine CISH microRNAs |
| url | https://www.mdpi.com/2073-4409/10/9/2250 |
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