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Nrf2 in Neoplastic and Non-Neoplastic Liver Diseases

Claudia Orrù1,2, Silvia Giordano1,2, Amedeo Columbano3

  • 1Department of Oncology, University of Torino, 10060 Candiolo, Italy.

Cancers
|October 15, 2020
PubMed

Insights

The Keap1/Nrf2 pathway protects cells from stress and liver damage. Its role in liver cancer and the mechanisms behind its activation in hepatocarcinogenesis require further investigation for targeted therapies.

Area of Science:

  • Cellular biology
  • Molecular mechanisms
  • Hepatology

Background:

  • The Keap1/Nrf2 pathway is a critical cellular defense against electrophilic and oxidative stress, crucial for cell survival.
  • This pathway's role in attenuating liver damage is significant, as oxidative stress is a key factor in hepatic pathologies.
  • However, the precise function of Nrf2 in non-cancerous liver cells and its activation mechanisms in liver cancer remain debated.

Purpose of the Study:

  • To review and analyze current knowledge on the role of Nrf2 in liver physiology and pathology, including hepatocellular carcinoma.
  • To critically examine findings from animal models regarding Nrf2 activation in hepatocarcinogenesis.
  • To address uncertainties surrounding the sustained activation of the Keap1/Nrf2 pathway in liver cancer and its therapeutic implications.

Main Methods:

  • Literature review and critical analysis of existing research.
  • Examination of data from animal models of liver disease and cancer.
  • Discussion of current understanding and identification of knowledge gaps.

Main Results:

  • Nrf2 activation is vital for cellular defense and mitigating liver damage.
  • The role of Nrf2 in non-neoplastic hepatocytes is not fully understood.
  • Mechanisms driving sustained Keap1/Nrf2 activation in hepatocarcinogenesis are unclear, impacting therapeutic strategies.

Conclusions:

  • Further research is needed to clarify Nrf2's dual role in liver health and cancer.
  • Understanding the specific mechanisms of Nrf2 activation in liver cancer is essential for developing effective treatments.
  • Animal model data provides insights but requires careful interpretation to answer outstanding questions.
Keywords:
Keap1/Nrf2 pathwayacute and chronic liver injuryliver regenerationmultistep hepatocarcinogenesis

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