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Research Progress on the Role of Natural Active Substances in Regulating Adenosine Pathway in Tumor Therapy

Xinyu Yang1,2, Xiaoyu Che1,2, Yaqin Li1,2

  • 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China.

Phytotherapy Research : PTR
|February 2, 2026
PubMed

Insights

Cancer immunotherapy faces challenges from adenosine, an immunosuppressive molecule in tumors. Natural compounds may offer a way to block adenosine's effects, potentially enhancing anti-cancer immunity and treatment.

Area of Science:

  • Oncology
  • Immunology
  • Biochemistry

Background:

  • Cancer incidence is rising globally, posing a significant public health challenge.
  • Tumor cells employ mechanisms to evade immune surveillance, with adenosine (ADO) being a key immunosuppressive factor.
  • Adenosine, produced from adenosine triphosphate (ATP) degradation, is abundant in the tumor microenvironment and promotes cancer progression.

Purpose of the Study:

  • To review adenosine's metabolic pathways and its role in the tumor microenvironment.
  • To explore the potential of natural compounds in modulating adenosine pathways for cancer immunotherapy.
  • To provide insights into novel strategies for cancer prevention and treatment.

Main Methods:

  • Literature review of adenosine metabolism in cancer.
  • Analysis of adenosine's immunosuppressive mechanisms via adenosine receptors (ARs).
  • Investigation of natural compounds (alkaloids, flavonoids, polyphenols) targeting the adenosine pathway.

Main Results:

  • Adenosine promotes tumor proliferation, migration, invasion, angiogenesis, and chemotherapy resistance.
  • Activated adenosine receptors (ARs) on tumor and immune cells suppress anti-tumor immunity.
  • Natural compounds demonstrate potential to interfere with adenosine production, transport, or signaling.

Conclusions:

  • Targeting the adenosine pathway is a promising strategy in tumor immunotherapy.
  • Natural compounds offer a potential avenue for reversing tumor-induced immunosuppression.
  • Modulating adenosine pathways with natural substances may lead to new cancer prevention and treatment approaches.
Keywords:
adenosineadenosine receptorsimmunosuppressionnatural active substancestumor microenvironment

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