ArticleCancer research and treatment2023
PD-L1 Upregulation by the mTOR Pathway in VEGFR-TKI-Resistant Metastatic Clear Cell Renal Cell Carcinoma.
Article in Cancer research and treatment, 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, 10 citations in OpenAlex.
- Hedgehog signaling activation rescues hypoxia-induced ferroptosis in human brain organoids.Neural regeneration research · 2026Article
- Case Report: No radiographic evidence of disease for 45 months in a patient with recurrent clear cell renal cell carcinoma treated with third-line combination therapy utilizing toripalimab and axitinib.Frontiers in immunology · 2026Article
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Bioinformatics Identification of Lactate-Associated Genes in Hepatocellular Carcinoma: G6PD's Role in Immune Modulation.Cancer medicine · 2025Article
- Significant increase in calcification and ossification observed after the second relapse of low-grade myofibroblast sarcoma treated with radiotherapy followed by anlotinib and toripalimab: a case report.Frontiers in immunology · 2025Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- IFITM3-mediated activation of TRAF6/MAPK/AP-1 pathways induces acquired TKI resistance in clear cell renal cell carcinoma.Investigative and clinical urology · 2024Article
- Prior Anti-Angiogenic TKI-Based Treatment as Potential Predisposing Factor to Nivolumab-Mediated Recurrent Thyroid Disorder Adverse Events in mRCC Patients: A Case Series.Biomedicines · 2023Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
purposeTyrosine kinase inhibitors (TKI) targeting vascular endothelial growth factor receptor (VEGFR) signaling pathways have been used for metastatic clear cell renal cell carcinoma (mCCRCC), but resistance to the drug develops in most patients. We aimed to explore the underlying mechanism of the TKI resistance with regard to programmed death-ligand 1 (PD-L1) and to investigate signaling pathway associated with the resistant mechanism. MATERIALS AND
methodsTo determine the mechanism of resistance, 10 mCCRCC patients from whom tumor tissues were harvested at both the pretreatment and the TKI-resistant post-treatment period were included as the discovery cohort, and their global gene expression profiles were compared. A TKI-resistant renal cancer cell line was established by long-term treatment with sunitinib.
resultsAmong differentially expressed genes in the discovery cohort, increased PD-L1 expression in post-treatment tissues was noted in four patients. Pathway analysis showed that PD-L1 expression was positively correlated with the mammalian target of rapamycin (mTOR) signaling pathway. The TKI-resistant renal cancer cells showed increased expression of PD-L1 and mTOR signaling proteins and demonstrated aggressive tumoral behaviour. Treatment with mTOR inhibitors down-regulated PD-L1 expression and suppressed aggressive tumoral behaviour, which was reversed with stimulation of the mTOR pathway.
conclusionThese results showed that PD-L1 expression may be increased in a subset of VEGFR-TKI-resistant mCCRCC patients via the mTOR pathway.
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