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Peer-reviewedCC BY 4.0Frontiers in Immunology

Toxic traditional Chinese medicines as hormetic immunomodulators in cancer: from toxicity-efficacy homology to translational opportunities

  • Qing Tong1,2
  • Zhiqiang Cai1
  1. 1Department of Oncology, The First Affiliated Hospital of Yangtze University
  2. 2Department of Pharmacology, Health Science Center, Yangtze University
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Abstract

The immunosuppressive tumor microenvironment (TIME) remains a major barrier to cancer immunotherapy, creating an urgent need for agents that can simultaneously remodel the TIME and potentiate immune checkpoint blockade. In this review, we propose the concept of “toxicity-efficacy homology”, which holds that the reactive chemical moieties of toxic traditional Chinese medicines (TCMs) serve as the shared structural basis for both their immunomodulatory activity and organ toxicity. Within a hormetic framework, these agents activate anti-tumor immunity within a low-dose “immunoactivation window”, whereas higher doses elicit non-specific toxicity. This review examines the molecular mechanisms, preclinical evidence, and clinical data for representative toxic TCMs, and highlights three interrelated translational bottlenecks: a narrow therapeutic window, low bioavailability, and quality-control challenges. To address these obstacles, a solution framework is outlined that integrates structural modification and prodrug design, intelligent nano-delivery, traditional compatibility-based detoxification, and a precision combination strategy guided by tumor immune phenotyping. Collectively, this review provides a conceptual basis for repositioning toxic TCMs from empirical “combating poison with poison” into mechanism-driven, evidence-based “attenuated toxicity and enhanced efficacy” immunotherapeutic agents.

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Cite

BibTeXRIS
BibTeX
@article{tong2026toxic,
  title = {{Toxic traditional Chinese medicines as hormetic immunomodulators in cancer: from toxicity-efficacy homology to translational opportunities}},
  author = {Qing Tong and Zhiqiang Cai},
  journal = {Frontiers in Immunology},
  year = {2026},
  month = oct,
  doi = {10.3389/fimmu.2026.1965726},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965726/full},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Toxic traditional Chinese medicines as hormetic immunomodulators in cancer: from toxicity-efficacy homology to translational opportunities
AU  - Qing Tong
AU  - Zhiqiang Cai
PY  - 2026
DA  - 2026/10/19
JO  - Frontiers in Immunology
DO  - 10.3389/fimmu.2026.1965726
UR  - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1965726/full
AB  - The immunosuppressive tumor microenvironment (TIME) remains a major barrier to cancer immunotherapy, creating an urgent need for agents that can simultaneously remodel the TIME and potentiate immune checkpoint blockade. In this review, we propose the concept of “toxicity-efficacy homology”, which holds that the reactive chemical moieties of toxic traditional Chinese medicines (TCMs) serve as the shared structural basis for both their immunomodulatory activity and organ toxicity. Within a hormetic framework, these agents activate anti-tumor immunity within a low-dose “immunoactivation window”, whereas higher doses elicit non-specific toxicity. This review examines the molecular mechanisms, preclinical evidence, and clinical data for representative toxic TCMs, and highlights three interrelated translational bottlenecks: a narrow therapeutic window, low bioavailability, and quality-control challenges. To address these obstacles, a solution framework is outlined that integrates structural modification and prodrug design, intelligent nano-delivery, traditional compatibility-based detoxification, and a precision combination strategy guided by tumor immune phenotyping. Collectively, this review provides a conceptual basis for repositioning toxic TCMs from empirical “combating poison with poison” into mechanism-driven, evidence-based “attenuated toxicity and enhanced efficacy” immunotherapeutic agents.
SN  - 1664-3224
ER  -