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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Bibliographic Details
Main Authors: Jianghua Shi, Luo Wang, Xuanwei Zeng, Chengzhi Xie, Zhaowei Meng, Anahit Campbell, Lulu Wang, Heli Fan, Huabing Sun
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
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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Summary: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.
ISSN:2296-889X