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An Oncogenic Hepatocyte-Induced Orthotopic Mouse Model of Hepatocellular Cancer Arising in the Setting of Hepatic Inflammation and Fibrosis
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Review article: pharmacological therapy for hepatocellular carcinoma with sorafenib and other oral agents

M Chaparro1, L González Moreno, M Trapero-Marugán

  • 1Department of Hepatology and Ciberehd, University Hospital La Princesa, Universidad Autónoma de Madrid, Madrid, Spain.

Alimentary Pharmacology & Therapeutics
|September 24, 2008
PubMed
Abstract

Insights

Sorafenib is a novel treatment prolonging survival for advanced hepatocellular carcinoma (HCC) patients. This targeted therapy offers a new standard for managing this challenging cancer when other treatments fail.

Area of Science:

  • Hepatocellular carcinoma (HCC) research
  • Oncology drug development
  • Molecular targeted therapy

Background:

  • Hepatocellular carcinoma (HCC) is a prevalent global malignancy with limited treatment options for unresectable cases.
  • Patients with advanced HCC face a poor prognosis, highlighting the urgent need for effective therapies.
  • Existing systemic chemotherapy approaches for HCC have shown minimal efficacy.

Purpose of the Study:

  • To review the mechanisms underlying hepatocarcinogenesis.
  • To discuss current systemic therapies for HCC.
  • To evaluate the role of Sorafenib in advanced HCC management.

Main Methods:

  • Comprehensive literature search of Medline database.
  • Inclusion of original research and review articles.
  • Evaluation of selected references for relevance.

Main Results:

  • Preclinical data indicate the involvement of the Raf/MAPK-ERK kinase (MEK)/Extracellular signal regulated kinase (ERK) pathway in HCC.
  • Tumorigenesis and metastasis in HCC are promoted by vascular endothelial growth factor (VEGF) due to high tumor vascularization.
  • Sorafenib inhibits tumor cell proliferation via Raf/MEK/ERK signaling and reduces angiogenesis by targeting VEGF receptors and platelet-derived growth factor receptor beta.

Conclusions:

  • Current therapeutic strategies offer limited benefit for advanced HCC patients.
  • Sorafenib is the first agent demonstrated to extend survival in advanced HCC.
  • Sorafenib establishes a new benchmark for systemic treatment in advanced hepatocellular carcinoma.

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