Precision-engineered PROTACs minimize off-tissue effects in cancer therapy
Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2024-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1505255/full |
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| _version_ | 1846160159922978816 |
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| author | Jianghua Shi Luo Wang Xuanwei Zeng Chengzhi Xie Zhaowei Meng Anahit Campbell Lulu Wang Heli Fan Huabing Sun Huabing Sun |
| author_facet | Jianghua Shi Luo Wang Xuanwei Zeng Chengzhi Xie Zhaowei Meng Anahit Campbell Lulu Wang Heli Fan Huabing Sun Huabing Sun |
| author_sort | Jianghua Shi |
| collection | DOAJ |
| description | Proteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies. Innovations such as PEGylation and nanotechnology also play a role in optimizing PROTAC efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges remain for clinical translation. |
| format | Article |
| id | doaj-art-e22f7234aa9c45069bff31c5a51836d0 |
| institution | Kabale University |
| issn | 2296-889X |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Molecular Biosciences |
| spelling | doaj-art-e22f7234aa9c45069bff31c5a51836d02024-11-22T09:18:09ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2024-11-011110.3389/fmolb.2024.15052551505255Precision-engineered PROTACs minimize off-tissue effects in cancer therapyJianghua Shi0Luo Wang1Xuanwei Zeng2Chengzhi Xie3Zhaowei Meng4Anahit Campbell5Lulu Wang6Heli Fan7Huabing Sun8Huabing Sun9National Engineering and Technology Research Center of Chirality Pharmaceutical, Lunan Pharmaceutical Group Co., Ltd., Linyi, ChinaState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, ChinaDepartment of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, United StatesState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaState Key Laboratory of Experimental Hematology, Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, The School of Pharmacy, Tianjin Medical University, Tianjin, ChinaDepartment of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, ChinaProteolysis-targeting chimeras (PROTACs) offer a groundbreaking approach to selectively degrade disease-related proteins by utilizing the ubiquitin-proteasome system. While this strategy shows great potential in preclinical and clinical settings, off-tissue effects remain a major challenge, leading to toxicity in healthy tissues. This review explores recent advancements aimed at improving PROTAC specificity, including tumor-specific ligand-directed PROTACs, pro-PROTACs activated in tumor environments, and E3 ligase overexpression strategies. Innovations such as PEGylation and nanotechnology also play a role in optimizing PROTAC efficacy. These developments hold promise for safer, more effective cancer therapies, though challenges remain for clinical translation.https://www.frontiersin.org/articles/10.3389/fmolb.2024.1505255/fullPROTACsoff-tissue effectsprecision-engineeredtargeted protein degradationPRO-PROTACredox-inducible |
| spellingShingle | Jianghua Shi Luo Wang Xuanwei Zeng Chengzhi Xie Zhaowei Meng Anahit Campbell Lulu Wang Heli Fan Huabing Sun Huabing Sun Precision-engineered PROTACs minimize off-tissue effects in cancer therapy Frontiers in Molecular Biosciences PROTACs off-tissue effects precision-engineered targeted protein degradation PRO-PROTAC redox-inducible |
| title | Precision-engineered PROTACs minimize off-tissue effects in cancer therapy |
| title_full | Precision-engineered PROTACs minimize off-tissue effects in cancer therapy |
| title_fullStr | Precision-engineered PROTACs minimize off-tissue effects in cancer therapy |
| title_full_unstemmed | Precision-engineered PROTACs minimize off-tissue effects in cancer therapy |
| title_short | Precision-engineered PROTACs minimize off-tissue effects in cancer therapy |
| title_sort | precision engineered protacs minimize off tissue effects in cancer therapy |
| topic | PROTACs off-tissue effects precision-engineered targeted protein degradation PRO-PROTAC redox-inducible |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2024.1505255/full |
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