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REVIEW article
Front. Mol. Biosci.
Sec. Molecular Diagnostics and Therapeutics
Volume 11 - 2024 |
doi: 10.3389/fmolb.2024.1505255
This article is part of the Research Topic Advances in PROTACs Promote the Development of Anticancer Therapy View all articles
Precision-engineered PROTACs minimize off-tissue effects in cancer therapy
Provisionally accepted- 1 Tianjin Medical University, Tianjin, China
- 2 Lunan Pharmaceutical Group Co. Ltd, Linyi, Shandong Province, China
- 3 Tianjin Medical University General Hospital, Tianjin, China
- 4 University of Wisconsin–Milwaukee, Milwaukee, Wisconsin, United States
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.
Keywords: PROTACs, off-tissue effects, precision-engineered, targeted protein degradation, PRO-PROTAC, redox-inducible
Received: 02 Oct 2024; Accepted: 28 Oct 2024.
Copyright: © 2024 Sun, Shi, Wang, Zeng, Xie, Meng, Campbell, Wang and Fan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Huabing Sun, Tianjin Medical University, Tianjin, China
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