ReviewCancer cell international2022
Modulation of the tumour microenvironment in hepatocellular carcinoma by tyrosine kinase inhibitors: from modulation to combination therapy targeting the microenvironment.
Review in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Survival benefits of different immunotherapies for hepatocellular carcinoma: a meta-analysis highlighting age, gender, etiology, and tumor burden.Frontiers in immunology · 2025Pooled it
- Calcium peroxide loaded liposomes reprogram hypoxic and acidic tumor microenvironment to overcome lenvatinib resistance in hepatocellular carcinoma.Materials today. Bio · 2026Article
- A multicenter dose-defining/expansion phase 1b study of first-line regorafenib plus pembrolizumab in patients with advanced hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- Immune profiling by bulk RNA-seq and multiplex immunofluorescence imaging across multiple cancer types.Frontiers in oncology · 2026Article
- Modeling hepatocellular carcinoma and its microenvironment on a chip.Cell death discovery · 2025Article
- Computational analysis of miRNA mediated KDR gene regulation and natural VEGFR2 inhibitors from Persicaria hydropiper in hepatocellular carcinoma.Scientific reports · 2025Article
- Piezo1: the Potential Novel Target for Radiation-induced Liver Fibrosis by Regulating FAP + fibroblasts.Molecular and cellular biochemistry · 2025Review
- MOF enhances the sensitivity and selectivity of sorafenib as an anticancer drug against hepatocellular carcinoma and colorectal cancer in vitro.Scientific reports · 2025Article
- Review
- Immunotherapy in GI Cancers: Lessons from Key Trials and Future Clinical Applications.Antibodies (Basel, Switzerland) · 2025Review
- The glycolytic characteristics of hepatocellular carcinoma and its interaction with the microenvironment: a comprehensive omics study.Journal of translational medicine · 2025Article
- Preoperative TACE with PD-1 inhibitors and TKIs in beyond "up-to-seven" hepatocellular carcinoma: a propensity score matched analysis.Frontiers in immunology · 2025Article
- Present and prospect of transarterial chemoembolization combined with tyrosine kinase inhibitor and PD-1 inhibitor for unresectable hepatocellular carcinoma.World journal of gastrointestinal oncology · 2024Article
- Therapeutic advances of targeting receptor tyrosine kinases in cancer.Signal transduction and targeted therapy · 2024Review
- Consistent efficacy of hepatic artery infusion chemotherapy irrespective of PD‑L1 positivity in unresectable hepatocellular carcinoma.Oncology letters · 2024Article
- Ferroptosis, pyroptosis and necroptosis in hepatocellular carcinoma immunotherapy: Mechanisms and immunologic landscape (Review).International journal of oncology · 2024Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Engineering materials for pyroptosis induction in cancer treatment.Bioactive materials · 2024Review
- The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2024Review
- High glucose-induced NCAPD2 upregulation promotes malignant phenotypes and regulates EMT via the Wnt/β-catenin signaling pathway in HCC.American journal of cancer research · 2024Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. Tyrosine kinase inhibitors (TKIs) remain the backbone of systematic therapy for advanced hepatocellular carcinoma. Sorafenib and lenvatinib are currently approved as first-line therapeutic drugs, and regorafenib and cabozantinib are applied as second-line treatments. With inhibition of angiogenesis as the main target, TKIs exert a profound effect on the tumour microenvironment (TME). The TME is a complex mixture of cellular and noncellular components surrounding the tumour mass, and is associated with tumour progression partially through the epithelial-mesenchymal transition. Specifically, the TME of HCC is characterized by profound extracellular matrix remodelling and an immunosuppressive microenvironment. The purpose of this review is to provide a summary of TME remodelling mediated by four Food and Drug Administration approved TKIs in HCC and thus summarize the rationale and potential targets for combination therapy. The modulatory effect of TKIs on the TME of HCC was reported to enhance the antitumour effect of TKIs through pyroptosis of macrophages and subsequent natural killer cell activation, T cell activation, regulatory T cell reduction in HCC. Meanwhile, TKIs also induce drug resistance via M2 polarization and accumulation, recruitment of tumour-associated neutrophils, and induction of the epithelial-mesenchymal transition. In conclusion, the effect of TKIs on TME can enhance its antitumour effect, but might also partially contribute to the drug resistance that hinders the progression of TKIs as treatment for HCC. Additionally, the effect of TKIs also provides the rationale for combination therapy, including combining TKIs with immune checkpoint inhibitors, to facilitate increased drug efficacy of TKIs.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.