ArticleCancer letters2018
EGFR-TKI-induced HSP70 degradation and BER suppression facilitate the occurrence of the EGFR T790 M resistant mutation in lung cancer cells.
Article in Cancer letters, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it, 23 citations in OpenAlex.
- Antibody-based regimens targeting PD-1/PD-L1 and VEGF/VEGFR in advanced or metastatic NSCLC: a meta-analysis of RCTs.Frontiers in immunology · 2026Pooled it
- Comparison of gefitinib plus chemotherapy versus gefitinib alone for advanced non‑small‑cell lung cancer: A meta analysis.Clinics (Sao Paulo, Brazil) · 2023Pooled it
- Persistent TOP1 cleavage complexes in drug-tolerant cells drive adaptive resistance to EGFR-targeted therapies in lung cancer.Science advances · 2026Article
- GRIP-Lung: Generative Model of Response to Drug-Induced Perturbation in Lung Cancer.International journal of molecular sciences · 2026Article
- Identification of a Prognostic Gene Signature for Chemoresistance Prediction in Lung Adenocarcinoma by Screening Mitochondrial Metabolism Gene Sets.International journal of molecular sciences · 2026Article
- The Confluence of Nanotechnology and Heat Shock Protein 70 in Pioneering Glioblastoma Multiforme Therapy: Forging Pathways Towards Precision Targeting and Transformation.Advances in pharmacological and pharmaceutical sciences · 2025Review
- EGFR-mediated HSP70 phosphorylation facilitates PCNA association with chromatin and DNA replication.Nucleic acids research · 2024Article
- Article
- An Undefined Interaction between Polyamines and Heat Shock Proteins Leads to Cellular Protection inMolecules (Basel, Switzerland) · 2023Review
- Molecular insights into the heat shock proteins of the human parasitic blood fluke Schistosoma mansoni.Parasites & vectors · 2022Article
- Genomic instability as a major mechanism for acquired resistance to EGFR tyrosine kinase inhibitors in cancer.Protein & cell · 2022Review
- DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.Molecular biology reports · 2021Review
- Heat Shock Proteins: Agents of Cancer Development and Therapeutic Targets in Anti-Cancer Therapy.Cells · 2019Review
- Combination of Anti-Cancer Drugs with Molecular Chaperone Inhibitors.International journal of molecular sciences · 2019Review
- The EGFR T790M Mutation Is Acquired through AICDA-Mediated Deamination of 5-Methylcytosine following TKI Treatment in Lung Cancer.Cancer research · 2018Article
Corrections and comments
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
Non-small cell lung cancer (NSCLC) patients harboring EGFR-activating mutations initially respond to EGFR tyrosine kinase inhibitors (EGFR-TKIs) and have shown favorable outcomes. However, acquired drug resistance to EGFR-TKIs develops in almost all patients mainly due to the EGFR T790 M mutation. Here, we show that treatment with low-dose EGFR-TKI results in the emergence of the EGFR T790 M mutation and in the reduction of HSP70 protein levels in HCC827 cells. Erlotinib treatment inhibits HSP70 phosphorylation at tyrosine 41 and increases HSP70 ubiquitination, resulting in HSP70 degradation. We show that EGFR-TKI treatment causes increased DNA damage and enhanced gene mutation rates, which are secondary to the EGFR-TKI-induced reduction of HSP70 protein. Importantly, HSP70 overexpression delays the occurrence of Erlotinib-induced EGFR T790 M mutation. We further demonstrate that HSP70 interacts with multiple enzymes in the base excision repair (BER) pathway and promotes not only the efficiency but also the fidelity of BER. Collectively, our findings show that EGFR-TKI treatment facilitates gene mutation and the emergence of EGFR T790 M secondary mutation by the attenuation of BER via induction of HSP70 protein degradation.
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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.