ArticleCancers2023
Integrin αvβ3 Is a Master Regulator of Resistance to TKI-Induced Ferroptosis in HER2-Positive Breast Cancer.
Article in Cancers, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
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Who cites it
15 citing papers in PubMed, 14 citations in OpenAlex.
- Unlocking the ferroptotic window: Lipidomic rewiring and metabolic addiction in EMT-driven breast cancer resistance.Cell death discovery · 2026Review
- Ferroptosis in breast cancer: From adipocyte-immune-iron regulation to therapeutic application.Clinical and translational medicine · 2026Review
- Targeting ATR and PI3Kα Pathways Promotes Ferroptosis inCancers · 2026Article
- Cell adhesion molecules as emerging regulators of ferroptosis: mechanisms and therapeutic opportunities in cancer.Apoptosis : an international journal on programmed cell death · 2026Review
- Crosstalk between ferroptosis and extracellular vesicles in cancer: from interaction to clinical application.Experimental hematology & oncology · 2026Review
- Integrin αvβ3 as a Non-Genomic Estrogen Receptor in Breast Cancer for Signaling Pathways and Crosstalk.Cells · 2025Review
- Natural Compounds as Modulators of Ferroptosis: Mechanistic Insights and Therapeutic Prospects in Breast Cancer.Biomolecules · 2025Review
- Defining the extracellular matrix for targeted immunotherapy in adult and pediatric brain cancer.NPJ precision oncology · 2025Article
- Integrins in Cancer Drug Resistance: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2025Review
- Ferroptosis - a potential feature underlying neratinib-induced colonic epithelial injury.Cancer chemotherapy and pharmacology · 2024Article
- The Role of αvβ3 Integrin in Cancer Therapy Resistance.Biomedicines · 2024Review
- Targeting ferroptosis: a promising strategy to overcome drug resistance in breast cancer.Frontiers in oncology · 2024Review
- Regulation of ferroptosis by PI3K/Akt signaling pathway: a promising therapeutic axis in cancer.Frontiers in cell and developmental biology · 2024Review
- Irreversible HER2 inhibitors overcome resistance to the RSL3 ferroptosis inducer in non-HER2 amplified luminal breast cancer.Cell death & disease · 2023Article
- Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Human epidermal growth factor receptor-2 (HER2)-targeting therapies provide clinical benefits for patients with HER2-positive breast cancer. However, the resistance to monotherapies invariably develops and leads to disease relapse and treatment failure. Previous studies have demonstrated a link between the potency of HER2-targeting tyrosine kinase inhibitors (TKIs) and their ability to induce an iron-dependent form of cell death called ferroptosis. The aim of this study was to understand the mechanisms of resistance to TKI-induced ferroptosis and identify novel approaches to overcome treatment resistance. We used mouse and human HER2-positive models of acquired TKI resistance to demonstrate an intimate link between the resistance to TKIs and to ferroptosis and present the first evidence that the cell adhesion receptor αvβ3 integrin is a critical mediator of resistance to TKI-induced ferroptosis. Our findings indicate that αvβ3 integrin-mediated resistance is associated with the re-wiring of the iron/antioxidant metabolism and persistent activation of AKT signalling. Moreover, using gene manipulation approaches and pharmacological inhibitors, we show that this "αvβ3 integrin addiction" can be targeted to reverse TKI resistance. Collectively, these findings provide critical insights into new therapeutic strategies to improve the treatment of advanced HER2-positive breast cancer patients.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.