ArticleScientific reports2016
Linifanib (ABT-869) Potentiates the Efficacy of Chemotherapeutic Agents through the Suppression of Receptor Tyrosine Kinase-Mediated AKT/mTOR Signaling Pathways in Gastric Cancer.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Association of Vascular Endothelial Growth Factor ( VEGF) Gene Polymorphisms With Gastric Cancer and Its Development, Prognosis, and Survival.Technology in cancer research & treatment · 2018Pooled it
- Apoptotic effect of linifanib on human ovarian cancer OVCAR3 cell line.Research in pharmaceutical sciences · 2025Article
- Linifanib alone and in combination with metronomic chemotherapy is active on cutaneous T-cell lymphoma cells by targeting the AKT/mTOR signaling pathway.Investigational new drugs · 2025Article
- Unveiling Indazole: Novel Synthetic Pathways and Biological Potentials.Medicinal chemistry (Shariqah (United Arab Emirates)) · 2025Review
- Role and value of the tumor microenvironment in the progression and treatment resistance of gastric cancer (Review).Oncology reports · 2025Review
- Click Chemistry and Targeted Degradation: A Winning Combination for Medicinal Chemists?ChemMedChem · 2023Review
- Omics- and Pharmacogenomic Evidence for the Prognostic, Regulatory, and Immune-Related Roles of PBK in a Pan-Cancer Cohort.Frontiers in molecular biosciences · 2021Article
- Charge-Transfer Complex of Linifanib with 2,3-dichloro-3,5-dicyano-1,4-benzoquinone: Synthesis, Spectroscopic Characterization, Computational Molecular Modelling and Application in the Development of Novel 96-microwell Spectrophotometric Assay.Drug design, development and therapy · 2021Article
- Associations of BNIP3 and DAPK1 gene polymorphisms with disease susceptibility, clinicopathologic features, anxiety, and depression in gastric cancer patients.International journal of clinical and experimental pathology · 2021Article
- Integrative transcriptomics analysis of lung epithelial cells and identification of repurposable drug candidates for COVID-19.European journal of pharmacology · 2020Article
- Synergistic activity of linifanib and irinotecan increases the survival of mice bearing orthotopically implanted human anaplastic thyroid cancer.American journal of cancer research · 2020Article
- A novel computational approach for drug repurposing using systems biology.Bioinformatics (Oxford, England) · 2018Article
- Thymoquinone induces cytotoxicity and reprogramming of EMT in gastric cancer cells by targeting PI3K/Akt/mTOR pathway.Journal of biosciences · 2017Article
- DDX5 promotes gastric cancer cell proliferation in vitro and in vivo through mTOR signaling pathway.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gastric cancer, highly dependent on tumor angiogenesis, causes uncontrolled lethality, in part due to chemoresistance. Here, we demonstrate that linifanib (ABT-869), a novel multi-targeted receptor tyrosine kinase inhibitor, markedly augments cytotoxicity of chemotherapies in human gastric cancer. ABT-869 and chemotherapeutic agents exhibited a strong synergy to inhibit the viability of several gastric cancer cell lines, with combination index values ranging from 0.017 to 0.589. Additionally, the combination of ABT-869 and chemotherapeutic agents led to remarkable suppression of vascular endothelial growth factor (VEGF)-induced angiogenesis in vitro and in vivo. Importantly, in a preclinical gastric cancer xenograft mouse model, drug co-treatments led to increased mouse survival as well as a synergistic reduction in tumor size and the inhibition of tumor angiogenesis. Mechanistic studies further revealed that all of the co-treatments containing ABT-869 resulted in decreased activation of the VEGF receptor, the epidermal growth factor receptor and the insulin growth factor receptor. Inhibition of these receptor tyrosine kinases consequently attenuated the activation of the downstream AKT/mTOR signaling pathway both in cultured gastric cancer cells and in gastric cancer xenografts. Collectively, our findings suggest that the addition of ABT-869 to traditional chemotherapies may be a promising strategy for the treatment of human gastric cancer.
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