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Deciphering the Anti-Tumor Mechanisms of Metformin Through Reprogramming of the Tumor Microenvironment

Ting Zeng1,2,3, Lemei Zheng1,2,3, Jianxia Wei1,2,3

  • 1NHC Key Laboratory of Carcinogenesis, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410078, China.

Cells
|July 13, 2026
PubMed

Insights

Metformin, a diabetes drug, shows anti-tumor effects by reprogramming the tumor microenvironment (TME). This review details how metformin impacts TME immunity, inflammation, and vascularization, offering new cancer therapy insights.

Area of Science:

  • Oncology
  • Pharmacology
  • Immunology

Background:

  • Metformin is a key type 2 diabetes drug with demonstrated anti-tumor properties.
  • Existing research primarily focuses on metformin's direct effects on tumor cells, neglecting its role within the tumor microenvironment (TME).
  • The TME is a complex system influencing tumor growth, progression, and treatment resistance through mechanisms like immune evasion and aberrant angiogenesis.

Purpose of the Study:

  • To systematically review metformin's impact on various TME components.
  • To elucidate the regulatory mechanisms underlying metformin's effects on the TME.
  • To explore metformin's potential in cancer therapy by understanding its TME-modulating actions.

Main Methods:

  • Systematic review of existing literature on metformin and the TME.
  • Analysis of signaling pathways regulated by metformin, including AMPK, PI3K/AKT/mTOR, and JNK.
  • Discussion of metformin's influence on immune, inflammatory, vascular, matrix, and metabolic aspects of the TME.

Main Results:

  • Metformin influences distinct components of the TME, impacting tumor progression.
  • The drug modulates immune responses, inflammation, angiogenesis, and metabolic functions within the TME.
  • Metformin's effects on the TME are mediated through various signaling pathways, suggesting multifaceted anti-tumor activity.

Conclusions:

  • Metformin actively reprograms the TME, contributing to its anti-tumor effects.
  • Understanding metformin's TME-mediated mechanisms can enhance its clinical application in cancer treatment.
  • This review provides a comprehensive overview for future research and therapeutic strategies involving metformin in oncology.
Keywords:
anti-tumor effectimmunomodulationmetformintumor microenvironmenttumor progression

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