ArticleCellular oncology (Dordrecht, Netherlands)2013
Insulin-like growth factor-1 receptor (IGF-1R) as a biomarker for resistance to the tyrosine kinase inhibitor gefitinib in non-small cell lung cancer.
Article in Cellular oncology (Dordrecht, Netherlands), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 2 of them syntheses that pooled it.
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Who cites it
52 citing papers in PubMed, 2 syntheses or guidelines pooled it, 89 citations in OpenAlex.
- RRM1 expression is associated with the outcome of gemcitabine-based treatment of non-small cell lung cancer patients--a short report.Cellular oncology (Dordrecht, Netherlands) · 2015Pooled it
- Insulin-like growth factor receptor 1 (IGF1R) expression and survival in non-small cell lung cancer patients: a meta-analysis.International journal of clinical and experimental pathology · 2014Pooled it
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- Intracellular cholesterol: new functions and therapeutic approaches in NSCLC EGFR-TKI resistance.Lipids in health and disease · 2025Review
- 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
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- An IGF-1R-mTORC1-SRPK2 signaling Axis contributes to FASN regulation in breast cancer.BMC cancer · 2022Article
- Actively targeted delivery of SN38 by ultrafine iron oxide nanoparticle for treating pancreatic cancer.Investigational new drugs · 2022Article
- MicroRNAs as the critical regulators of tyrosine kinase inhibitors resistance in lung tumor cells.Cell communication and signaling : CCS · 2022Review
- Preclinical Models for Acquired Resistance to Third-Generation EGFR Inhibitors in NSCLC: Functional Studies and Drug Combinations Used to Overcome Resistance.Frontiers in oncology · 2022Review
- The role of IGF-pathway biomarkers in determining risks, screening, and prognosis in lung cancer.Oncotarget · 2022Review
- The Extracellular Matrix in Pancreatic Cancer: Description of a Complex Network and Promising Therapeutic Options.Cancers · 2021Review
- Insulin-like growth factor 1 promotes proliferation and invasion of papillary thyroid cancer through the STAT3 pathway.Journal of clinical laboratory analysis · 2020Article
- Effects of hyperinsulinemia on acquired resistance to epidermal growth factor receptor-tyrosine kinase inhibitor via the PI3K/AKT pathway in non-small cell lung cancer cellsOncology letters · 2020Article
- Identification of genetic alterations associated with primary resistance to EGFR-TKIs in advanced non-small-cell lung cancer patients with EGFR sensitive mutations.Cancer communications (London, England) · 2019Article
- IGFBP7 Drives Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibition in Lung Cancer.Cancers · 2019Article
- MiR-30a-5p confers cisplatin resistance by regulating IGF1R expression in melanoma cells.BMC cancer · 2018Article
- Suppressor of cytokine signalling-2 limits IGF1R-mediated regulation of epithelial-mesenchymal transition in lung adenocarcinoma.Cell death & disease · 2018Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundThe insulin-like growth factor-1 receptor (IGF-1R) pathway is known to play a role in the acquisition of resistance to epidermal growth factor receptor (EGFR)-specific tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). However, its exact role in TKI resistance has so far remained unclear. Here, we interrogated the hypothesis that the IGF-1R may serve as a biomarker for, and may play a role in, intrinsic resistance to the EGFR-specific TKI gefitinib in NSCLC.
methodsTotal-IGF-1R and phosphorylated (p)-IGF-1R expression levels were related to gefitinib sensitivity in 23 NSCLC cell lines. This sensitivity was re-evaluated after knocking down IGF-1R expression and after IGF-1R up-regulation through exogenous IGF-1 expression. The utility of IGF-1R expression as a predictive biomarker was also evaluated by immunohistochemistry (IHC) in 98 primary NSCLC samples from patients treated with gefitinib.
resultsSeventeen of the cell lines tested were resistant to gefitinib, whereas 3 cell lines were sensitive. The three remaining cell lines showed intermediate values. Thirteen resistant cell lines were found to be positive for total-IGF-1R expression, while all the sensitive cell lines were negative, resulting in a positive predictive value (PPV) of 81% for total-IGF-1R to predict resistance. Seven resistant cell lines exhibited high p-IGF-1R levels, whereas all 3 sensitive cell lines were negative for p-IGF-1R, resulting in a PPV of 100% for p-IGF-1R to predict resistance. Neither a knock-down of IGF-1R expression nor an activation of the IGF1-R pathway through exogenous IGF-1 expression affected gefitinib sensitivity. In primary NSCLC tissues, IGF-1R expression was found to be significantly higher in patients with progressive disease, i.e., showing gefitinib resistance, as compared to those with a complete or partial response.
conclusionsIGF-1R acts as a predictor for resistance to gefitinib in NSCLC cell lines and NSCLC patients, but does not seem to play a role in the intrinsic resistance to this drug. High total-IGF-1R and p-IGR-1R levels may predict such a resistance. Since the underlying mechanism does not appear to be related to proliferation induction, alternative pathways should be explored.
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