Signaling pathways in hepatocellular carcinoma

Teresa Garcia-Lezana, Juan Luis Lopez-Canovas, Augusto Villanueva

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

59 Scopus citations


Despite the recent introduction of new effective systemic agents, the survival of patients with hepatocellular carcinoma (HCC) at advanced stages remains dismal. This underscores the need for new therapies, which has spurred extensive research on the identification of the main drivers of pathway de-regulation as a source of novel therapeutic targets. Frequently altered pathways in HCC involve growth factor receptors (e.g., VEGFR, FGFR, TGFA, EGFR, IGFR) and/or its cytoplasmic intermediates (e.g., PI3K-AKT-mTOR, RAF/ERK/MAPK) as well as key pathways in cell differentiation (e.g., Wnt/β-catenin, JAK/STAT, Hippo, Hedgehog, Notch). Somatic mutations, chromosomal aberrations and epigenetic changes are common mechanisms for pathway deregulation in HCC. Aberrant pathway activation has also been explored as a biomarker to predict response to specific therapies, but currently, these strategies are not implemented when deciding systemic therapies in HCC patients. Beyond the well-established molecular cascades, there are numerous emerging signaling pathways also deregulated in HCC (e.g., tumor microenvironment, non-coding RNA, intestinal microbiota), which have opened new avenues for therapeutic exploration.

Original languageEnglish
Title of host publicationMechanisms and Therapy of Liver Cancer
EditorsDevanand Sarkar, Paul B. Fisher
PublisherAcademic Press Inc.
Number of pages39
ISBN (Print)9780128240304
StatePublished - Jan 2021

Publication series

NameAdvances in Cancer Research
ISSN (Print)0065-230X
ISSN (Electronic)2162-5557


  • Growth factors
  • HCC
  • Hedgehog
  • Hippo
  • Notch
  • Signaling pathways
  • TGF-β
  • Wnt/β-catenin


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