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A Three-Dimensional Spheroid Model to Investigate the Tumor-Stromal Interaction in Hepatocellular Carcinoma
Published on: September 30, 2021
Hepatocellular Carcinoma: Basic and Transitional Research
1Department of Gastroenterology, Changzheng Hospital, Second Military Medical University, Shanghai, PR China.
Background:
Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. The outcome of HCC therapy depends on the stage of HCC. Early-stage HCC patients can be cured with radical treatment approaches, whereas no standard treatment regimens can be recommended for patients with advanced disease.
Summary:
In-depth basic research into the molecular mechanisms of HCC has contributed to the development of novel therapeutic agents. This article reviews several key classes of novel therapeutic agents that are under development, including molecular-targeted therapies, cancer stem cell (CSC)-based therapy and differentiation therapy.
Key Message:
A greater understanding of the molecular pathogenesis of HCC has contributed to the development of novel therapeutic agents. This article reviews several key classes of novel therapeutic agents that are under development, including molecular-targeted therapies, CSC-based therapy and differentiation therapy.
Practical Implications:
Molecular-targeted therapies based on signaling pathways involved in hepatocarcinogenesis and progression are being evaluated in several clinical trials. There are three main categories of targeted agents: tyrosine kinase inhibitors (TKIs), monoclonal antibodies and enzyme inhibitors. The best-established agent is sorafenib, a non-specific TKI that is accepted as first-line therapy for specific patients. Other similar agents under investigation include erlotinib, linifanib and brivanib. CSC-based therapies are still in the earlier stages of development and include a neutralizing anti-CD44 antibody, small interfering RNA to suppress epithelial cell adhesion molecular levels, a neutralizing anti-CD13 antibody and a CD13 inhibitor. An important point is that CSC-targeted therapy should be combined with conventional therapies to achieve complete tumor regression. Differentiation therapy is defined as a strategy that induces malignant reversion of tumor cells. Hepatocyte nuclear factor 4α or 1α, important transcriptional factors for hepatocyte differentiation and phenotype maintenance, have shown significant antitumor effects by inducing differentiation of both non-CSCs and CSCs in HCC towards a hepatocyte-like phenotype.
