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Updated: Mar 15, 2026

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IDO1 regulating ROS rhythm reveals glycogenolysis/PPP as a cancer treatment target

Nannan Zhou1, Zheng Ling1, Xiankai Cao1

  • 1Department of Immunology and National Key Laboratory of Common Mechanism Research for Major Diseases, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Nature Chemical Biology
|March 14, 2026
PubMed

Insights

Cancer cells exhibit rhythmic reactive oxygen species (ROS) oscillations. Loss of this rhythm promotes tumor growth, but dual inhibition of IDO1 and AhR pathways can prolong survival by disrupting ROS rhythm.

Area of Science:

  • Oncology
  • Cell Biology
  • Biochemistry

Background:

  • Reactive oxygen species (ROS) dynamics in cancer cells often show rhythmic oscillations.
  • The influence of ROS rhythmicity on tumorigenesis and therapeutic responses is not fully understood.

Purpose of the Study:

  • To investigate the role of ROS rhythmicity in cancer development and treatment.
  • To explore the mechanisms underlying ROS rhythm regulation and its impact on tumor growth.

Main Methods:

  • Analysis of ROS rhythmicity and rhythm loss in tumor samples.
  • Investigating the interaction between indoleamine 2,3-dioxygenase 1 (IDO1), KEAP1, and ROS levels.
  • Examining the role of the aryl hydrocarbon receptor (AhR)-mediated pathway in hypoxic tumor microenvironments.
  • Assessing the therapeutic efficacy of dual IDO1 and AhR inhibition in a mouse model.

Main Results:

  • Tumor samples displayed both ROS rhythmicity and rhythm loss.
  • Under low ROS, IDO1 degrades in the nucleus; under high ROS, IDO1 forms an active holoenzyme in the cytosol, enhancing ROS clearance.
  • Hypoxic tumors lose ROS rhythmicity and activate the AhR pathway for ROS management, favoring tumor growth.
  • Dual inhibition of IDO1 and AhR significantly improved survival in NSG mice.

Conclusions:

  • Disruption of ROS rhythm is a critical factor in tumor progression.
  • The interplay between IDO1, AhR, and ROS dynamics dictates tumor behavior.
  • Targeting ROS rhythm disruption offers a promising therapeutic strategy for cancer treatment.

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