ArticleLaboratory investigation; a journal of technical methods and pathology2019
Epithelial-mesenchymal transition as a mechanism of resistance to tyrosine kinase inhibitors in clear cell renal cell carcinoma.
Article in Laboratory investigation; a journal of technical methods and pathology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Estimation of Future Patient Populations Eligible for Radioligand Therapies in the EU and the UK: A Modelling Study.The Lancet regional health. Europe · 2026Article
- Article
- IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.Investigative and clinical urology · 2024Article
- Article
- Inhibiting stanniocalcin 2 reduces sunitinib resistance of Caki-1 renal cancer cells under hypoxia condition.Annals of medicine and surgery (2012) · 2023Article
- ZDHHC2-Mediated AGK Palmitoylation Activates AKT-mTOR Signaling to Reduce Sunitinib Sensitivity in Renal Cell Carcinoma.Cancer research · 2023Article
- Cancer-associated fibroblast-derived secreted phosphoprotein 1 contributes to resistance of hepatocellular carcinoma to sorafenib and lenvatinib.Cancer communications (London, England) · 2023Article
- Primary and acquired resistance to first-line therapy for clear cell renal cell carcinoma.Cancer drug resistance (Alhambra, Calif.) · 2023Review
- Molecular mechanisms of resistance to tyrosine kinase inhibitor in clear cell renal cell carcinoma.International journal of urology : official journal of the Japanese Urological Association · 2022Review
- Resistance to tyrosine kinase inhibitors promotes renal cancer progression through MCPIP1 tumor-suppressor downregulation and c-Met activation.Cell death & disease · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
- Advances in Renal Cell Carcinoma Drug Resistance Models.Frontiers in oncology · 2022Review
- Elevated SNRPA1, as a Promising Predictor Reflecting Severe Clinical OutcomeFrontiers in immunology · 2022Article
- Eosinophilic features in clear cell renal cell carcinoma correlate with outcomes of immune checkpoint and angiogenesis blockade.Journal for immunotherapy of cancer · 2021Article
- Identification of DNA methylation signatures associated with poor outcome in lower-risk Stage, Size, Grade and Necrosis (SSIGN) score clear cell renal cell cancer.Clinical epigenetics · 2021Article
- Replisome genes regulation by antitumor miR-101-5p in clear cell renal cell carcinoma.Cancer science · 2020Article
- Involvement of the TNF-α Pathway in TKI Resistance and Suggestion of TNFR1 as a Predictive Biomarker for TKI Responsiveness in Clear Cell Renal Cell Carcinoma.Journal of Korean medical science · 2020Article
- Circular RNA hsa_circ_001895 serves as a sponge of microRNA-296-5p to promote clear cell renal cell carcinoma progression by regulating SOX12.Cancer science · 2020Article
- Epigenetic Alterations in Renal Cell Cancer With TKIs Resistance: From Mechanisms to Clinical Applications.Frontiers in genetics · 2020Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tyrosine kinase inhibitors (TKIs) are widely accepted as treatment for metastatic clear cell renal cell carcinoma (ccRCC). However, most patients eventually experience disease progression despite TKI treatment, even if the initial response is favorable. To define the underlying mechanism of TKI resistance, 10 TKI-treated metastatic ccRCC cases in which tumor samples were harvested before treatment and immediately after disease progression were examined. Gene expression profiles and copy number variations of matched pre- and post-treatment tumor samples were investigated. Altered biologic characteristics were confirmed in sunitinib-resistant ccRCC cell lines, which were generated by long-term treatment with sunitinib-containing media. Gene transcript levels related to the cell cycle and epithelial-mesenchymal transition (EMT) were significantly upregulated in the treated tumor samples compared with the pre-treatment samples. The mitotic count and sarcomatoid component were significantly increased in treated tumor samples. Alteration of EMT-related genes was also demonstrated in a sunitinib-resistant ccRCC cell line that showed enhanced migration and invasion compared to the parent cell line. siRNA-induced inhibition of EMT-related gene expression significantly suppressed the migration and invasion capacity of TKI-resistant cell lines. The present study shows that both ccRCC cases that progressed after TKI treatment and sunitinib-resistant ccRCC cell lines demonstrated alteration of EMT-related gene expression and enhancement of EMT-related behavior. These results suggest that EMT may explain the aggressive behavior of TKI-resistant ccRCC.
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