ArticleBritish journal of cancer2019
Integrated analysis of multiple receptor tyrosine kinases identifies Axl as a therapeutic target and mediator of resistance to sorafenib in hepatocellular carcinoma.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 45 citations in OpenAlex.
- Second-line cabozantinib after sorafenib treatment for advanced hepatocellular carcinoma: a subgroup analysis of the phase 3 CELESTIAL trial.ESMO open · 2020Trial
- AXL at the nexus of therapeutic resistance, tumor vascularization, and immune evasion in cancer.iScience · 2026Review
- 1D228 Attenuates Sorafenib Resistance in Renal Cell Carcinoma Models by Dual Targeting c-Met and AXL.Cells · 2026Article
- Advancing Systemic Treatment beyond First Line for Advanced Hepatocellular Carcinoma.Current oncology reports · 2026Review
- Noncanonical EZH2 activity cooperates with FOXM1 to drive tumorigenesis and advanced progression in HCC.Clinical and molecular hepatology · 2026Article
- [Role of Receptor Tyrosine Kinase AXL in Cancer Targeted Therapy Drug Resistance].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- A phase 1b, multicentre, dose escalation, safety and pharmacokinetics study of tilvestamab (BGB149) in relapsed, platinum-resistant, high-grade serous ovarian cancer (PROC) patients.British journal of cancer · 2025Article
- Sex hormone-binding globulin restrains hepatic fibrosis via inhibition of Tgfβ expression.Journal of molecular medicine (Berlin, Germany) · 2025Article
- Inhibition of the Caveolin-1 pathway promotes apoptosis and overcomes pan-tyrosine kinase inhibitor resistance in hepatocellular carcinoma.Cell death & disease · 2025Article
- Regulation of lung cancer initiation and progression by the stem cell determinant Musashi.eLife · 2025Article
- AXL signaling in cancer: from molecular insights to targeted therapies.Signal transduction and targeted therapy · 2025Review
- Targeting AXL induces tumor-intrinsic immunogenic response in tyrosine kinase inhibitor-resistant liver cancer.Cell death & disease · 2024Article
- GAS6/TAM Axis as Therapeutic Target in Liver Diseases.Seminars in liver disease · 2024Article
- From MASH to HCC: the role of Gas6/TAM receptors.Frontiers in immunology · 2024Review
- Reciprocal interactions between malignant cells and macrophages enhance cancer stemness and M2 polarization in HBV-associated hepatocellular carcinoma.Theranostics · 2024Article
- NFX1-123: A potential therapeutic target in cervical cancer.Journal of medical virology · 2023Article
- Article
- The GSK3β/Mcl-1 axis is regulated by both FLT3-ITD and Axl and determines the apoptosis induction abilities of FLT3-ITD inhibitors.Cell death discovery · 2023Article
- Altered expression of AXL receptor tyrosine kinase in gastrointestinal cancers: a promising therapeutic target.Frontiers in oncology · 2023Review
- Synergism of the receptor tyrosine kinase Axl with ErbB receptors mediates resistance to regorafenib in hepatocellular carcinoma.Frontiers in oncology · 2023Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundAberrant activation of Axl is implicated in the progression of hepatocellular carcinoma (HCC). We explored the biologic significance and preclinical efficacy of Axl inhibition as a therapeutic strategy in sorafenib-naive and resistant HCC.
methodsWe evaluated Axl expression in sorafenib-naive and resistant (SR) clones of epithelial (HuH7) and mesenchymal origin (SKHep-1) using antibody arrays and confirmed tissue expression. We tested the effect of Axl inhibition with RNA-interference and pharmacologically with R428 on a number of phenotypic assays.
resultsAxl mRNA overexpression in cell lines (n = 28) and RNA-seq tissue datasets (n = 373) correlated with epithelial-to-mesenchymal transition (EMT). Axl was overexpressed in HCC compared to cirrhosis and normal liver. We confirmed sorafenib resistance to be associated with EMT and enhanced motility in both HuH7-SR and SKHep-1-SR cells documenting a 4-fold increase in Axl phosphorylation as an adaptive feature of chronic sorafenib treatment in SKHep-1-SR cells. Axl inhibition reduced motility and enhanced sensitivity to sorafenib in SKHep-1SR cells. In patients treated with sorafenib (n = 40), circulating Axl levels correlated with shorter survival.
conclusionsSuppression of Axl-dependent signalling influences the transformed phenotype in HCC cells and contributes to adaptive resistance to sorafenib, providing a pre-clinical rationale for the development of Axl inhibitors as a measure to overcome sorafenib resistance.
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