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Updated: Jul 26, 2025

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ANO1-Mediated Inhibition of Cancer Ferroptosis Confers Immunotherapeutic Resistance through Recruiting

Fangli Jiang1, Keren Jia1, Yang Chen1

  • 1Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, P. R. China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|June 21, 2023
PubMed

Insights

ANO1 protein is a key driver of poor outcomes and immunotherapy resistance in gastrointestinal cancers. Inhibiting ANO1 shows promise for enhancing cancer treatment effectiveness.

Area of Science:

  • Oncology
  • Immunology
  • Molecular Biology

Background:

  • Immunotherapy faces challenges in gastrointestinal (GI) cancers due to limited response rates and acquired resistance.
  • Identifying novel biomarkers and therapeutic targets is crucial for improving GI cancer treatment outcomes.

Purpose of the Study:

  • To investigate the role of ANO1 in GI cancer progression and its impact on immunotherapy response.
  • To explore ANO1 as a potential therapeutic target for overcoming treatment resistance in GI cancers.

Main Methods:

  • Analysis of clinical cohorts and multi-omics data.
  • Functional experiments involving ANO1 knockdown and inhibition in various GI cancer models (cell lines, xenografts).
  • Investigation of molecular mechanisms involving ferroptosis, PI3K-Akt signaling, and cancer-associated fibroblast recruitment.

Main Results:

  • ANO1 amplification or high expression correlates with poor prognosis and immunotherapy resistance in GI cancer patients.
  • ANO1 inhibition suppresses tumor growth, metastasis, and invasion across multiple models.
  • ANO1 promotes an immune-suppressive tumor microenvironment by inhibiting ferroptosis and recruiting cancer-associated fibroblasts, leading to anti-PD-1 resistance.

Conclusions:

  • ANO1 plays a critical role in remodeling the tumor immune microenvironment and mediating resistance to immunotherapy in GI cancers.
  • Targeting ANO1 can enhance the effectiveness of immunotherapy and overcome resistance, presenting a promising strategy for precision treatment.
Keywords:
ANO1cancer-associated fibroblastsferroptosisgastrointestinal cancersimmunotherapeutic resistance

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