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Related Experiment Video

Updated: Nov 20, 2025

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Hepatocellular carcinoma.

Josep M Llovet1,2,3, Robin Kate Kelley4, Augusto Villanueva5

  • 1Mount Sinai Liver Cancer Program, Division of Liver Diseases, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. josep.llovet@mssm.edu.

Nature Reviews. Disease Primers
|January 22, 2021
PubMed
Summary
This summary is machine-generated.

Liver cancer, primarily hepatocellular carcinoma (HCC), poses a global threat. Advances in systemic therapies and ongoing clinical trials offer new hope for managing advanced HCC and improving patient outcomes.

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Area of Science:

  • Hepatology and Oncology
  • Molecular Pathogenesis
  • Clinical Trial Research

Background:

  • Liver cancer, particularly hepatocellular carcinoma (HCC), represents a significant global health burden, projected to exceed 1 million cases by 2025.
  • Hepatitis B and C virus infections are primary risk factors, with non-alcoholic steatohepatitis (NASH) emerging as a key driver in Western populations, presenting unique molecular characteristics.
  • A subset of HCCs (~25%) harbor actionable mutations, yet clinical translation remains limited, complicating non-invasive diagnostic approaches that require molecular insights.

Purpose of the Study:

  • To review the current landscape of liver cancer, focusing on hepatocellular carcinoma (HCC).
  • To highlight advancements in the management of advanced HCC, including approved systemic therapies and ongoing clinical trials.
  • To discuss the evolving role of molecular pathogenesis and diagnostic challenges in HCC.

Main Methods:

  • Review of current literature on liver cancer epidemiology, risk factors, and molecular pathogenesis.
  • Analysis of approved systemic therapies for advanced HCC based on phase III trials and accelerated FDA approvals.
  • Examination of ongoing clinical trials exploring novel combination therapies, including immunotherapies and targeted agents.

Main Results:

  • Six systemic therapies (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib, ramucirumab) are approved for advanced HCC.
  • Three additional therapies received accelerated FDA approval, demonstrating efficacy.
  • Numerous clinical trials are investigating novel combinations, including immunotherapy and anti-angiogenic agents.

Conclusions:

  • Significant progress has been made in systemic therapy for advanced HCC, altering patient management strategies.
  • Future research focusing on combination therapies holds promise for further improving outcomes across all stages of HCC.
  • Addressing molecular heterogeneity and improving non-invasive diagnostics are crucial for advancing HCC care.