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April 6, 2026Advanced Functional Materials

Tumor Microenvironment‐Responsive PROTAC Prodrugs: A Pioneering Strategy for Precision Cancer Therapy

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Authors

HYHong YaoYZYu Shrike ZhangMLMeng Liu

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Overview

This review examines tumor microenvironment-responsive PROTAC prodrugs, highlighting their efficacy and potential in cancer treatments.

Key Points

  • To explore innovative strategies for developing PROTAC prodrugs that selectively target tumor microenvironments for cancer therapy.
  • Systematic review of TME-responsive PROTAC prodrug design
  • Analysis of structure-activity relationships
  • Evaluation of activation kinetics and therapeutic efficacy
  • Discussion of combination strategies with other treatment modalities
  • Innovative prodrugs remain inactive until activated by TME-specific stimuli
  • Different mechanisms utilized include enzyme cleavage, GSH sensitivity, hypoxia activation, ROS response, and pH responsiveness
  • Emerging combination strategies enhance therapeutic outcomes with reduced off-target effects

Cite This Study

Yao et al. (2026) studied this question.

synapsesocial.com/papers/69d34e1e9c07852e0af97bb7https://doi.org/10.1002/adfm.202527321
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