ArticleScientific reports2017
Blocking autophagy improves the anti-tumor activity of afatinib in lung adenocarcinoma with activating EGFR mutations in vitro and in vivo.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 60 citations in OpenAlex.
- Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Exploratory Study to Evaluate the Efficacy and Safety of HAD-B1 for Dose-Finding in EGFR Mutation Positive and Locally Advanced or Metastatic NSCLC Subjects Who Need Afatinib Therapy.Integrative cancer therapiesTrial
- Stanniocalcin 2-Induced Autophagy Confers Resistance of Lung Cancer Cells to EGFR Inhibition via the ERK/Beclin 1 Signaling.Cancer medicine · 2026Article
- Evaluating the Therapeutic Potential of MRT68921 and Afatinib in Three-Dimensional Models of Epithelial Ovarian Cancer.Cancers · 2026Article
- Advances in understanding the mechanisms underlying acquired resistance to third-generation tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in cell and developmental biology · 2026Review
- An overview of autophagy inhibition as a potential clinical strategy in cancer therapy.Molecular pharmacology · 2025Review
- Is Autophagy Targeting a Valid Adjuvant Strategy in Conjunction with Tyrosine Kinase Inhibitors?Cancers · 2024Review
- Promoting reactive oxygen species accumulation to overcome tyrosine kinase inhibitor resistance in cancer.Cancer cell international · 2024Review
- 4″-Alkyl EGCG Derivatives Induce Cytoprotective Autophagy Response by Inhibiting EGFR in Glioblastoma Cells.ACS omega · 2024Article
- Effect of regulatory cell death on the occurrence and development of head and neck squamous cell carcinoma.Biomarker research · 2023Review
- Therapeutic potential of TRPM8 channels in cancer treatment.Frontiers in pharmacology · 2023Review
- Altered splicing of ATG16-L1 mediates acquired resistance to tyrosine kinase inhibitors of EGFR by blocking autophagy in non-small cell lung cancer.Molecular oncology · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Downregulation of fibulin-4 inhibits autophagy and promotes the sensitivity of esophageal squamous cell carcinoma cells to apatinib by activating the Akt-mTOR signaling pathway.Thoracic cancer · 2022Article
- Neuroprotective Effect of Astersaponin I against Parkinson's Disease through Autophagy Induction.Biomolecules & therapeutics · 2021Article
- [Construction and Validation of Prognostic Risk Score Model of Autophagy Related Genes in Lung Adenocarcinoma].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2021Article
- Afatinib induces pro-survival autophagy and increases sensitivity to apoptosis in stem-like HNSCC cells.Cell death & disease · 2021Article
- Recent Research Progress of Chiral Small Molecular Antitumor-Targeted Drugs Approved by the FDA From 2011 to 2019.Frontiers in oncology · 2021Review
- Adaptive response of resistant cancer cells to chemotherapy.Cancer biology & medicine · 2020Review
- Determining the effects of trastuzumab, cetuximab and afatinib by phosphoprotein, gene expression and phenotypic analysis in gastric cancer cell lines.BMC cancer · 2020Article
- Inhibition of autophagy flux by sertraline attenuates TRAIL resistance in lung cancer via death receptor 5 upregulation.International journal of molecular medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Afatinib, a second-generation tyrosine kinase inhibitor (TKI), has been approved for the treatment of advanced EGFR-mutant non-small cell lung cancer (NSCLC). However, afatinib's clinical application is still hampered by acquired resistance. Recently, autophagy is considered as an important mechanism of resistance to TKI. Herein, we investigated the autophagy induction as well as its influence on anti-lung adenocarcinoma activity of afatinib in two activating EGFR-mutants H1975 and H1650 cells. First, Growth inhibition and caspase-dependent apoptosis were observed in afatinib-treated H1975 and H1650 cells. Then we confirmed afatinib-induced autophagy in H1975 and H1650 cells. Importantly, autophagy inhibition using chloroquine (CQ) and 3-MA enhanced the cytotoxicity of afatinib, elucidating the cytoprotective role of autophagy in lung adenocarcinoma therapy with afatinib. Further study suggested that Akt/mTOR and Erk signaling pathways were involved in afatinib-induced autophagy, and reactive oxygen species (ROS) acted as an intracellular transducer regulating both autophagy and apoptosis in afatinib-treated H1975 and H1650 cells. Moreover, the in vivo experiment in xenograft model using H1975 cell line confirmed the enhanced anti-lung adenocarcinoma efficacy of afatinib when combined with autophagy inhibitor CQ. Thus, blocking autophagy may be a promising strategy to overcome resistance and increase sensitivity to afatinib in lung adenocarcinoma harboring activating EGFR mutations.
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