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Updated: Apr 15, 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
Systemic therapy for hepatocellular carcinoma
James J Harding1, Ghassan K Abou-Alfa2
1Memorial Sloan-Kettering Cancer Center, New York, NY, USA. hardinj1@mskcc.org.
Abstract:
The prognosis is poor for patients with advanced hepatocellular carcinoma (HCC). Sorafenib is the only accepted standard of care for advanced disease. The benefits of this agent are modest and the precise mechanism of antitumor activity in HCC is unknown. Since the approval of sorafenib, there has been intense investigation into strategies that block angiogenic pathways. Unfortunately, the results of three randomized phase III trials that compared newer anti-angiogenic treatments to sorafenib failed to demonstrate their superiority or non-inferiority. Thus, there remains a critical need for both continued molecular characterization and aggressive drug development in hepatocellular carcinoma.
Insights
Advanced hepatocellular carcinoma (HCC) has a poor prognosis, with sorafenib offering modest benefits. New anti-angiogenic drugs have not surpassed sorafenib, highlighting the need for further molecular research and drug development in HCC.
Area of Science:
- Hepatocellular carcinoma (HCC) research
- Cancer therapeutics
- Molecular oncology
Background:
- Advanced hepatocellular carcinoma (HCC) carries a poor prognosis.
- Sorafenib is the current standard of care, but its benefits are modest and its mechanism of action in HCC remains unclear.
- Despite extensive research into anti-angiogenic pathways, newer treatments have not proven superior to sorafenib in phase III trials.
Purpose of the Study:
- To review the current landscape of advanced hepatocellular carcinoma treatment.
- To highlight the limitations of existing therapies, including sorafenib.
- To emphasize the urgent need for novel therapeutic strategies and molecular understanding in HCC.
Main Methods:
- Review of clinical trial data for advanced hepatocellular carcinoma.
- Analysis of sorafenib's efficacy and mechanism of action.
- Evaluation of recent anti-angiogenic therapies in HCC.
Main Results:
- Sorafenib remains the sole standard of care for advanced HCC, offering limited clinical benefit.
- Three major phase III trials failed to establish the superiority or non-inferiority of newer anti-angiogenic agents compared to sorafenib.
- The precise antitumor mechanisms of sorafenib in HCC are yet to be fully elucidated.
Conclusions:
- There is a critical unmet need for improved therapeutic options for advanced hepatocellular carcinoma.
- Continued molecular characterization of HCC is essential for developing more effective treatments.
- Aggressive drug development targeting novel pathways is imperative for advancing HCC patient care.
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