ArticleBritish journal of cancer2020
Nintedanib inhibits intrahepatic cholangiocarcinoma aggressiveness via suppression of cytokines extracted from activated cancer-associated fibroblasts.
Article in British journal of cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 62 citations in OpenAlex.
- Convergent Microenvironment Linking Idiopathic Pulmonary Fibrosis and Lung Cancer.Expert reviews in molecular medicine · 2026Review
- Nintedanib Attenuates Epidural Fibrosis after Laminectomy in Rats.Journal of Korean Neurosurgical Society · 2026Article
- Article
- Gemcitabine-cisplatin plus durvalumab in advanced intrahepatic cholangiocarcinoma: effectiveness outcomes and characterization of the tumor microenvironment.Hepatology international · 2026Article
- Nintedanib enhances the antitumor efficacy of pd-1 blockade, potentially through inhibition of myeloid-derived suppressor cells and cancer-associated fibroblasts.Cancer immunology, immunotherapy : CII · 2026Article
- Cancer-Associated Fibroblasts in the Treatment of Intrahepatic Cholangiocarcinoma: Present and Prospects.Journal of hepatocellular carcinoma · 2026Review
- Integrative analysis of scRNA-seq and RNA-seq to investigate the prognostic value of lactylation and fibroblast-related genes in intrahepatic cholangiocarcinoma.Scientific reports · 2025Article
- Cancer-associated fibroblasts in the tumor microenvironment: heterogeneity, crosstalk mechanisms, and therapeutic implications.Molecular cancer · 2025Review
- Nintedanib enhances tumor cell radiosensitivity by promoting ferroptosis and modulating the ATF4/SLC7A11/GSH axis.Cancer biology & medicine · 2025Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- The Effect of Inhaled Ozone Therapy in Two-Hit Rat Model of Lipopolysaccharides-Induced Acute Lung Injury and Bleomycin-Induced Pulmonary Fibrosis.The protein journal · 2025Article
- Interplay between cancer-associated fibroblasts and dendritic cells: implications for tumor immunity.Frontiers in immunology · 2025Review
- Molecular Mechanisms of Gemcitabine Resistance in Cholangiocarcinoma.Oncology research · 2025Review
- Innovative Nanomedicine Delivery: Targeting Tumor Microenvironment to Defeat Drug Resistance.Pharmaceutics · 2024Review
- Potential of Mac-2-binding protein glycan isomer as a new therapeutic target in pancreatic cancer.Cancer science · 2024Article
- Single‑agent nintedanib suppresses metastatic osteosarcoma growth by inhibiting tumor vascular formation.Oncology letters · 2024Article
- Lnc-PKNOX1-1 inhibits tumor progression in cutaneous malignant melanoma by regulating NF-κB/IL-8 axis.Carcinogenesis · 2023Article
- Meta-analysis: clinical features and treatments of lung cancer in combined pulmonary fibrosis and emphysema.Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG · 2023Article
- Automated Analysis for the Prevalence of Cancer-Associated Fibroblasts in Resected Specimens of Intrahepatic Cholangiocarcinoma is a Simple and Reliable Evaluation System.Annals of surgical oncology · 2023Article
- Lobe-specific responses of TRAMP mice dorsolateral prostate following celecoxib and nintedanib therapy.Journal of molecular histology · 2023Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIntrahepatic cholangiocarcinoma (ICC) is a malignancy that is challenging to treat. Fibroblasts in ICC tissues have been identified as cancer-associated fibroblasts (CAFs) that promote the malignant behaviour of ICC cells. An antifibrotic drug nintedanib has been reported to suppress activated hepatic stellate cells in liver fibrosis.
methodsWe investigated whether nintedanib could suppress the cancer-promoting effect of CAFs derived from ICC tissues in vitro and in vivo.
resultsCAFs promoted the proliferation and invasion of ICC cells. Nintedanib suppressed activated CAFs expressing α-smooth muscle actin (α-SMA) and inhibited the ICC-promoting effects of CAFs. Nintedanib greatly reduced the levels of cancer-promoting cytokines, such as interleukin (IL)-6 (IL-6) and IL-8, secreted by CAFs. An in vivo study demonstrated that nintedanib reduced xenografted ICC growth and activated CAFs expressing α-SMA, and that combination therapy with nintedanib and gemcitabine against CAFs and ICC cells showed the strongest inhibition of tumour growth compared with the control and single-treatment groups.
conclusionsNintedanib inhibited the cancer-promoting effect of CAFs via the suppression of CAF activation and secretion of cancer-promoting cytokines. Our findings suggest that therapeutic strategies combining conventional cytotoxic agents with nintedanib targeting CAFs are promising for overcoming refractory ICC with activated CAFs.
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