ArticlePharmacology research & perspectives2023
Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer.
Article in Pharmacology research & perspectives, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 8 citations in OpenAlex.
- Molecular signatures under hexavalent chromium, particulate matter 2.5, and cigarette smoking exposures.Discover oncology · 2025Article
- Elevated expression and secretion of TGF-α contribute to Temozolomide resistance in human glioblastoma cells.Cancer cell international · 2025Article
- Mechanisms of Resistance to ALK Inhibitors and Corresponding Treatment Strategies in Lung Cancer.International journal of general medicine · 2025Review
- MicroRNA-mediated autophagy regulation in thyroid cancer drug resistance.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Association of inflammatory cytokines with type 2 diabetes mellitus and diabetic nephropathy: a bidirectional Mendelian randomization study.Frontiers in medicine · 2024Article
- Progress on angiogenic and antiangiogenic agents in the tumor microenvironment.Frontiers in oncology · 2024Review
- Dysregulated Signalling Pathways Driving Anticancer Drug Resistance.International journal of molecular sciences · 2023Review
- Autocrine EGF and TGF-α promote primary and acquired resistance to ALK/c-Met kinase inhibitors in non-small-cell lung cancer.Pharmacology research & perspectives · 2023Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Drug resistance severely limits the clinical therapeutic value of molecularly targeted drugs. Growth factors gain a tremendous amount of focus due to the ability to promote drug resistance in non-small-cell lung cancer (NSCLC). However, whether tumor cells themselves can mediate drug resistance by secreting growth factors needs further clarification. Here, we first screened growth factors to identify autocrine epidermal growth factor (EGF) and transforming growth factor alpha (TGF-α) that caused primary resistance to the ALK inhibitor TAE684 in H3122 cells and the c-MET-specific inhibitor SGX-523 in EBC-1 cells. Next, we discovered increased autocrine production of EGF and TGF-α in established acquired resistant H3122/TR and EBC-1/SR cells. Importantly, overexpression of EGF and TGF-α in two NSCLC cell lines produced resistance to TAE684 and SGX-523. Clinically, NSCLC patients with high expression of EGF and TGF-α developed primary resistance to crizotinib. Mechanistically, autocrine EGF and TGF-α activated EGFR signaling pathways to survive targeted c-Met and ALK inhibition. Furthermore, combined treatment with gefitinib circumvented EGF- and TGF-α-mediated primary and acquired resistance to TAE684/SGX-523. Taken together, these results suggested increased autocrine EGF and TGF-α conferred primary and acquired resistance to ALK/c-Met kinase inhibitors in NSCLC.
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