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Updated: Jan 10, 2026

An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
Published on: September 12, 2019
Integrated therapies for targeting the microenvironment of hepatocellular carcinoma
Shriraam Karunakaran1, Mohan Krishna Ghanta2, Anusha Lakshmi Cheetiyar3
1Department of Biochemistry, MVJ Medical College and Research Hospital, Bangalore, Karnataka 562114, India.
Abstract:
Hepatocellular carcinoma (HCC) microenvironments (MEs) are composed of immune and non-immune components that drive tumor progression and treatment resistance. This narrative review summarizes recent progress in systemic therapies combined with liver-directed approaches as a new frontier in metastatic HCC treatment. Immune checkpoint inhibitors (tremelimumab and durvalumab) in combination with small- molecule agents (lenvatinib and cabozantinib) enhance T-cell activation and improve progression-free survival in HCC. Epigenetic inhibitors and RNA-based therapeutics target the HCC ME and increase the efficacy of immunotherapy. Additionally, cellular therapy targeting agents like glypican-3 (GPC3) for chimeric antigen receptor T (CAR-T) cells have shown promising results. HCC ME has distinct immune subtypes exhibiting different responses to treatments, which complicates biomarker selection and treatment timing. Personalized therapy based on ME is the future path in HCC management.
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