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AANG: A natural compound formulation for targeting macrophage-myofibroblast transition in non-small-cell lung

Max Kam-Kwan Chan1, Philip Chiu-Tsun Tang1, Zoey Zeyuan Ji1

  • 1Department of Anatomical and Cellular Pathology, State Key Laboratory of Translational Oncology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.

Phytomedicine : International Journal of Phytotherapy and Phytopharmacology
|February 14, 2026
PubMed

Insights

Researchers identified macrophage-myofibroblast transition (MMT) as a source of pro-tumorigenic cancer-associated fibroblasts (CAFs) in non-small-cell lung cancer (NSCLC). A optimized Traditional Chinese Medicine (TCM) formulation, AANG, effectively blocked MMT and cancer progression in preclinical models.

Area of Science:

  • Oncology
  • Immunology
  • Pharmacology

Background:

  • Cancer-associated fibroblasts (CAFs) are key components of the tumor microenvironment (TME), exhibiting heterogeneity that hinders therapeutic development.
  • Macrophage-myofibroblast transition (MMT) has been identified as a significant source of pro-tumoral CAFs in non-small-cell lung cancer (NSCLC).

Purpose of the Study:

  • To investigate the role of Smad signaling in MMT within NSCLC.
  • To evaluate the efficacy of an optimized Traditional Chinese Medicine (TCM) formulation, AANG, in blocking MMT and subsequent cancer progression.

Main Methods:

  • Spatial single-cell bioinformatics analysis of clinical NSCLC samples.
  • In vitro studies using bone marrow-derived macrophages (BMDM) treated with optimized AANG.
  • In vivo evaluation of AANG in mouse models of NSCLC (LLC and A549 xenografts).

Main Results:

  • Spatial single-cell bioinformatics revealed Smad3 activation and Smad7 reduction in MMT macrophages in NSCLC.
  • Optimized AANG modulated TGF-β1/Smad3/Smad7 signaling, effectively blocking MMT in BMDM in vitro.
  • AANG demonstrated efficacy in blocking MMT-derived cancer progression in vivo without observable side effects.

Conclusions:

  • MMT is a critical pathway for pro-tumoral CAF generation in NSCLC.
  • Optimized AANG shows potential as a novel therapeutic agent for targeting MMT-derived CAFs in NSCLC.
  • AANG may be the first natural compound formulation to block MMT-derived pro-tumoral CAF formation in clinical NSCLC.
Keywords:
Cancer-associated fibroblastsMacrophage-myofibroblast transitionNatural compound therapyNon-small-cell lung cancerSmad3/Smad7 signalingTumor microenvironment

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