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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
Huabing Sun Huabing Sun 1*Jianghua Shi Jianghua Shi 2Luo Wang Luo Wang 1Xuanwei Zeng Xuanwei Zeng 1Chengzhi Xie Chengzhi Xie 1Zhaowei Meng Zhaowei Meng 3Anahit Campbell Anahit Campbell 4Lulu Wang Lulu Wang 1Heli Fan Heli Fan 1
  • 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

The final, formatted version of the article will be published soon.

    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

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.