Targeted therapies for hepatocellular carcinoma
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Updated: May 13, 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
Augusto Villanueva1, Josep M Llovet
1HCC Translational Research Laboratory, Barcelona-Clinic Liver Cancer Group, Institut d'Investigacions Biomèdiques August Pi i Sunyer, Liver Unit, Hospital Clínic, Barcelona, Catalonia, Spain.
Abstract:
Unlike most solid tumors, the incidence and mortality of hepatocellular carcinoma (HCC) have increased in the United States and Europe in the past decade. Most patients are diagnosed at advanced stages, so there is an urgent need for new systemic therapies. Sorafenib, a tyrosine kinase inhibitor (TKI), has shown clinical efficacy in patients with HCC. Studies in patients with lung, breast, or colorectal cancers have indicated that the genetic heterogeneity of cancer cells within a tumor affect its response to therapeutics designed to target specific molecules. When tumor progression requires alterations in specific oncogenes (oncogene addiction), drugs that selectively block their products might slow tumor growth. However, no specific oncogene addictions are yet known to be implicated in HCC progression, so it is important to improve our understanding of its molecular pathogenesis. There are currently many clinical trials evaluating TKIs for HCC, including those tested in combination with (eg, erlotinib) or compared with (eg, linifanib) sorafenib as a first-line therapy. For patients who do not respond or are intolerant to sorafenib, TKIs such as brivanib, everolimus, and monoclonal antibodies (eg, ramucirumab) are being tested as second-line therapies. There are early stage trials investigating the efficacy for up to 60 reagents for HCC. Together, these studies might change the management strategy for HCC, and combination therapies might be developed for patients with advanced HCC. Identification of oncogenes that mediate tumor progression, and trials that monitor their products as biomarkers, might lead to personalized therapy; reagents that interfere with signaling pathways required for HCC progression might be used to treat selected populations, and thereby maximize the efficacy and cost benefit.
Insights
Hepatocellular carcinoma (HCC) treatment needs new systemic therapies due to rising incidence and late diagnoses. Understanding molecular drivers and exploring targeted agents, including tyrosine kinase inhibitors (TKIs), may personalize treatment for advanced HCC.
Area of Science:
- Hepatobiliary oncology
- Molecular targeted therapy
- Cancer genomics
Background:
- Hepatocellular carcinoma (HCC) incidence and mortality are rising in the US and Europe, with most patients diagnosed at advanced stages.
- Current systemic therapies for HCC, like sorafenib (a tyrosine kinase inhibitor), show efficacy but face challenges due to tumor genetic heterogeneity.
- Understanding the molecular pathogenesis and identifying specific oncogene addictions are crucial for developing effective HCC treatments.
Purpose of the Study:
- To review the current landscape of systemic therapies for hepatocellular carcinoma (HCC).
- To highlight the need for improved understanding of HCC molecular pathogenesis to guide personalized treatment strategies.
- To discuss ongoing and future clinical trials evaluating tyrosine kinase inhibitors (TKIs) and combination therapies for advanced HCC.
Main Methods:
- Review of current clinical trials and literature on systemic therapies for HCC.
- Analysis of the role of genetic heterogeneity and oncogene addiction in cancer treatment response.
- Exploration of emerging therapeutic strategies, including TKIs and combination regimens.
Main Results:
- Numerous clinical trials are evaluating TKIs, both as monotherapy and in combination, for first- and second-line HCC treatment.
- Identification of specific oncogenes driving HCC progression could lead to targeted therapies and personalized treatment approaches.
- Combination therapies and novel reagents targeting signaling pathways show promise for managing advanced HCC.
Conclusions:
- Advancements in understanding HCC molecular pathogenesis are essential for developing more effective and personalized systemic therapies.
- Ongoing trials with various tyrosine kinase inhibitors and combination strategies may significantly alter the management of advanced HCC.
- Biomarker identification and targeted interventions hold the potential to improve treatment efficacy and cost-effectiveness for selected HCC patient populations.
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