ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Susceptibility of Mitophagy-Deficient Tumors to Ferroptosis Induction by Relieving the Suppression of Lipid Peroxidation.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Mitophagy in cisplatin-induced kidney injury: regulatory mechanisms and therapeutic targets.Annals of medicine · 2026Review
- Subcellular regulation of ferroptosis: roles of individual intracellular organelles and cross talk.American journal of physiology. Cell physiology · 2026Review
- Metabolism, autophagy, and cell death: The triangular axis in tumor survival and therapeutic resistance.Redox biology · 2026Review
- An Avalanche Effect Nanomodulator Triggers Cascade Ferroptosis/Cuproptosis for Immunosuppressive Microenvironment Remodeling.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Magneto-NIR-II-Programmed Cascade Nanozymes Unlocking Blood-Brain Barrier Translocation and Autophagic Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Diosgenin presents a novel role in promoting diabetic wound healing: A mechanism involving Sirt6/Nrf2-mediated inhibition of ferroptosis.Journal of pharmaceutical analysis · 2026Article
- Article
- Ferroptosis in colorectal cancer: Molecular mechanisms and regulatory crosstalk with therapeutic prospects (Review).Oncology reports · 2026Review
- The dual role of the crosstalk between autophagy and ferroptosis in lung cancer treatment: Advances in mechanisms and therapeutic strategies (Review).International journal of molecular medicine · 2026Review
- A bezafibrate bearing Pt(IV) prodrug triggers ferroptosis via modulating lipid metabolism in lung cancer cells.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2026Article
- Ferroptosis-autophagy crosstalk in bladder cancer: mechanisms and therapeutic implications.Molecular cancer · 2026Review
- Multifaceted Anticancer Activity of Flavanone/Chromanone Intermediates for Five-Membered Heterocyclic Derivatives: Targeting Oxidative Stress, Apoptosis, and MAPK Signaling in Colorectal Cancer.Molecules (Basel, Switzerland) · 2026Article
- Milk fat globule-EGF factor 8/ATP-binding cassette subfamily E member 1 axis maintains mitophagy flux homeostasis to suppress ferroptosis in acute pancreatitis.Clinical and translational medicine · 2026Article
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Methyltransferase-like 3/14-mediated mResearch (Washington, D.C.) · 2026Article
- Molecular mechanism and potential role of mitophagy in breast cancer.Journal of Cancer · 2026Review
- Patient-Derived Organoids as a Platform to Decipher and Overcome Radioresistance: From the Tumor Microenvironment to Radiosensitizer Discovery.Current oncology (Toronto, Ont.) · 2025Review
- Article
- Ferroptosis, autophagy, and mitochondrial dynamics: Front burners in cancer therapeutics.World journal of clinical oncology · 2025Article
- Advances in novel cell death mechanisms in breast cancer: intersecting perspectives on ferroptosis, cuproptosis, disulfidptosis, and pyroptosis.Molecular cancer · 2025Review
Corrections and comments
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Authors and funding
14 authors.
Funding
Abstract
The identification of ferroptosis-sensitive cancers is critical for the application of ferroptosis-inducing therapies in cancer therapy. Here, patient-derived organoid screening models of colorectal cancer are established to identify tumors that are sensitive to ferroptosis-inducing therapy. This study discovers that patient-derived tumors characterized by mitophagy deficiency are hypersensitive to ferroptosis-inducing therapies. Mechanistically, a novel negative feedback regulatory pathway of lipid peroxidation is identified, which is one of the important intrinsic anti-ferroptosis mechanisms of cancer cells. Lipid peroxidation-mediated endoplasmic reticulum stress transcriptionally upregulates Parkin to promote mitophagy through ATF4. Mitophagy limits the generation of lipid peroxidation products and subsequently inhibits ferroptosis by inhibiting the accumulation of mitochondrial ROS. Mitophagy-deficient tumors lack this anti-ferroptotic mechanism, unleashing the generation of lipid peroxidation and potent ferroptotic cell death induced by erastin, RSL3, cysteine deprivation, radiotherapy, and immunotherapy. More importantly, ferroptosis-inducing therapy selectively inhibits the growth and distant metastasis of mitophagy-deficient tumors in vivo. In summary, patient-derived organoids of colorectal cancer patients for screening ferroptosis-sensitive tumors are established, providing a paradigm for identifying that patient-derived tumors are sensitive to ferroptosis-inducing therapies. This study concludes that mitophagy-deficient tumors are vulnerable to ferroptosis induction, which may lead to the development of new therapeutic strategies for tumors deficient in mitophagy.
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