ArticlePloS one2013
Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Differential transcriptional effects of EGFR inhibitors.PloS one · 2014Pooled it
- Autophagy-Apoptosis Crosstalk in Cancer: Mechanisms, Signaling Pathways, and Therapeutic Targeting.Cancers · 2026Review
- Stanniocalcin 2-Induced Autophagy Confers Resistance of Lung Cancer Cells to EGFR Inhibition via the ERK/Beclin 1 Signaling.Cancer medicine · 2026Article
- Repurposing Antimalarials for Oral Cancer: Selective Efficacy of Hydroxychloroquine on Gingival Squamous Cell Carcinoma.International journal of molecular sciences · 2025Article
- Gefitinib induces apoptosis in Caco-2 cells via ER stress-mediated mitochondrial pathways and the IRE1α/JNK/p38 MAPK signaling axis.Medical oncology (Northwood, London, England) · 2025Article
- The role of autophagy in cancer: from molecular mechanism to therapeutic window.Frontiers in immunology · 2025Review
- Liposomal Formulation of Hydroxychloroquine Can Inhibit Autophagy In Vivo.Pharmaceutics · 2024Article
- Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications.Medical oncology (Northwood, London, England) · 2024Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- The role and implication of autophagy in cholangiocarcinoma.Cell death discovery · 2023Review
- EGFR-T790M Mutation-Derived Interactome Rerouted EGFR Translocation Contributing to Gefitinib Resistance in Non-Small Cell Lung Cancer.Molecular & cellular proteomics : MCP · 2023Article
- Review
- Co-delivery of doxorubicin and hydroxychloroquine via chitosan/alginate nanoparticles for blocking autophagy and enhancing chemotherapy in breast cancer therapy.Frontiers in pharmacology · 2023Article
- Targeting Both Autophagy and Immunotherapy in Breast Cancer Treatment.Metabolites · 2022Review
- Non-coding RNAs associated with autophagy and their regulatory role in cancer therapeutics.Molecular biology reports · 2022Review
- miR-4487 Enhances Gefitinib-Mediated Ubiquitination and Autophagic Degradation of EGFR in Non-Small Cell Lung Cancer Cells by Targeting USP37.Cancer research and treatment · 2022Article
- Understanding the Role of Autophagy in Cancer Formation and Progression Is a Real Opportunity to Treat and Cure Human Cancers.Cancers · 2021Review
- Small Molecules Targeting Programmed Cell Death in Breast Cancer Cells.International journal of molecular sciences · 2021Review
- Erlotinib Promotes Ligand-Induced EGFR Degradation in 3D but Not 2D Cultures of Pancreatic Ductal Adenocarcinoma Cells.Cancers · 2021Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Gefitinib (Iressa(®), ZD1839) is a small molecule inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase. We report on an early cellular response to gefitinib that involves induction of functional autophagic flux in phenotypically diverse breast cancer cells that were sensitive (BT474 and SKBR3) or insensitive (MCF7-GFPLC3 and JIMT-1) to gefitinib. Our data show that elevation of autophagy in gefitinib-treated breast cancer cells correlated with downregulation of AKT and ERK1/2 signaling early in the course of treatment. Inhibition of autophagosome formation by BECLIN-1 or ATG7 siRNA in combination with gefitinib reduced the abundance of autophagic organelles and sensitized SKBR3 but not MCF7-GFPLC3 cells to cell death. However, inhibition of the late stage of gefitinib-induced autophagy with hydroxychloroquine (HCQ) or bafilomycin A1 significantly increased (p<0.05) cell death in gefitinib-sensitive SKBR3 and BT474 cells, as well as in gefitinib-insensitive JIMT-1 and MCF7-GFPLC3 cells, relative to the effects observed with the respective single agents. Treatment with the combination of gefitinib and HCQ was more effective (p<0.05) in delaying tumor growth than either monotherapy (p>0.05), when compared to vehicle-treated controls. Our results also show that elevated autophagosome content following short-term treatment with gefitinib is a reversible response that ceases upon removal of the drug. In aggregate, these data demonstrate that elevated autophagic flux is an early response to gefitinib and that targeting EGFR and autophagy should be considered when developing new therapeutic strategies for EGFR expressing breast cancers.
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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.