ArticleMolecular carcinogenesis2016
Inhibition of IGF1R signaling abrogates resistance to afatinib (BIBW2992) in EGFR T790M mutant lung cancer cells.
Article in Molecular carcinogenesis, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 71 citations in OpenAlex.
- Fc-Dependent Targeting of the GAS6-MERTK Axis With Monoclonal and Bispecific Antibodies Overcomes Drug Resistance Across EGFR Mutations in Exons 19, 20, and 21.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In Situ Amplified Mutational mRNA Imaging Using a Spatially Confined CRISPR Nanoplatform.Angewandte Chemie (International ed. in English) · 2026Article
- Pisces: A multi-modal data augmentation approach for drug combination synergy prediction.Cell genomics · 2025Article
- Strategies to Overcome Resistance to Osimertinib in EGFR-Mutated Lung Cancer.International journal of molecular sciences · 2025Review
- Mining of candidate genes related to body size in Chinese native pig breeds based on public data.Scientific reports · 2025Article
- Targeted Management: Unlocking the Crucial Role of PROTACs in Cancer Treatment.Current drug discovery technologies · 2025Review
- Deciphering genetic characteristics of South China and North China indigenous pigs through selection signatures.BMC genomics · 2024Article
- Afatinib plus PEM and CBDCA overcome osimertinib resistance in EGFR-mutated NSCLC with high thrombospondin-1 expression.Cancer science · 2024Article
- Single cell lineage tracing reveals clonal dynamics of anti-EGFR therapy resistance in triple negative breast cancer.Genome medicine · 2024Article
- Role of Insulin-like Growth Factor-1 Receptor in Tobacco Smoking-Associated Lung Cancer Development.Biomedicines · 2024Review
- Research progress on the role of bypass activation mechanisms in resistance to tyrosine kinase inhibitors in non-small cell lung cancer.Frontiers in oncology · 2024Review
- Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators.Cancers · 2023Review
- Drugging IGF-1R in cancer: New insights and emerging opportunities.Genes & diseases · 2023Review
- Novel considerations on EGFR-based therapy as a contributor to cancer cell death in NSCLC.Frontiers in oncology · 2023Review
- Natural Products in Preventing Tumor Drug Resistance and Related Signaling Pathways.Molecules (Basel, Switzerland) · 2022Review
- Drug resistance of targeted therapy for advanced non-small cell lung cancer harbored EGFR mutation: from mechanism analysis to clinical strategy.Journal of cancer research and clinical oncology · 2021Review
- Phase 1b Open-Label Trial of Afatinib Plus Xentuzumab (BI 836845) in Patients WithJTO clinical and research reports · 2021Article
- Cooperation and Interplay between EGFR Signalling and Extracellular Vesicle Biogenesis in Cancer.Cells · 2020Review
- Inhibiting insulin and mTOR signaling by afatinib and crizotinib combination fosters broad cytotoxic effects in cutaneous malignant melanoma.Cell death & disease · 2020Article
- Identification of MMP1 as a potential gene conferring erlotinib resistance in non-small cell lung cancer based on bioinformatics analyses.Hereditas · 2020Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation have benefited from treatment of reversible EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib. Acquisition of a secondary mutation in EGFR T790M is the most common mechanism of resistance to first generation EGFR TKIs, resulting in therapeutic failure. Afatinib is a second generation of EGFR TKI that showed great efficacy against tumors bearing the EGFR T790M mutation, but it failed to show the improvement on overall survival of lung cancer patients with EGFR mutations possibly because of novel acquired resistance mechanisms. Currently, there are no therapeutic options available for lung cancer patients who develop acquired resistance to afatinib. To identify novel resistance mechanism(s) to afatinib, we developed afatinib resistant cell lines from a parental human-derived NSCLC cell line, H1975, harboring both EGFR L858R and T790M mutations. We found that activation of the insulin-like growth factor 1 receptor (IGF1R) signaling pathway contributes to afatinib resistance in NSCLC cells harboring the T790M mutation. IGF1R knockdown not only significantly sensitizes resistant cells to afatinib, but also induces apoptosis in afatinib resistance cells. In addition, combination treatment with afatinib and linsitinib shows more than additive effects on tumor growth in in vivo H1975 xenograft. Therefore, these finding suggest that IGF1R inhibition or combination of EGFR-IGF1R inhibition strategies would be potential ways to prevent or potentiate the effects of current therapeutic options to lung cancer patients demonstrating resistance to either first or second generation EGFR TKIs.
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