What question did this study set out to answer?

To determine whether concurrent activation of β-catenin and Nrf2 drives hepatocellular carcinoma development and to evaluate therapeutic vulnerabilities in this tumor subset.

February 5, 2021HepatologyOpen Access

Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications

View Full Paper

Ask AI

Bookmark

Authors

JTJunyan TaoUniversity of Pittsburgh YKYekaterina KrutsenkoUniversity of Pittsburgh AMAkshata MogheMarine Biological Laboratory

Discussion

Member takes

Implication

Preclinical study demonstrates that coactivating beta-catenin and Nrf2 drives hepatocellular carcinoma in mice, indicating therapeutic sensitivity to mTOR inhibitors.

Key Points

To determine whether concurrent activation of β-catenin and Nrf2 drives hepatocellular carcinoma development and to evaluate therapeutic vulnerabilities in this tumor subset.
Analyzed public human hepatocellular carcinoma datasets to evaluate co-occurrence of CTNNB1 mutations alongside NFE2L2/KEAP1 mutations or Nrf2 activation gene signatures.
Coexpressed mutant T41A-CTNNB1 with wild-type, G31A-, or T80K-mutant NFE2L2 in mice and assessed tumor development, mortality, and RNA-sequencing pathway concordance.
Administered the mTOR inhibitor everolimus (5 mg/kg diet ad libitum) to mice bearing NFE2L2-CTNNB1 hepatocellular carcinoma to measure tumor response.
Concomitant CTNNB1 mutations and Nrf2 activation occurred in 9% of human hepatocellular carcinoma cases, driven partly by mutations in NFE2L2 or KEAP1.
Coexpression of mutant CTNNB1 with mutant NFE2L2, but not wild-type NFE2L2, induced lethal hepatocellular carcinoma in mice within 12 to 14 weeks.
Everolimus treatment led to a greater than 50% decrease in tumor burden in preclinical NFE2L2-CTNNB1 hepatocellular carcinoma mouse models.

Cite This Study

Tao et al. (2021) studied this question.

synapsesocial.com/papers/6aaf78be341a24f03fde69fd https://doi.org/10.1002/hep.31730

View Full Paper

Ask AI

Bookmark

Implication

Preclinical study demonstrates that coactivating beta-catenin and Nrf2 drives hepatocellular carcinoma in mice, indicating therapeutic sensitivity to mTOR inhibitors.

Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications

Discussion

Member takes

Implication

Key Points

Cite This Study

Nuclear factor erythroid 2–related factor 2 and β‐Catenin Coactivation in Hepatocellular Cancer: Biological and Therapeutic Implications

Discussion

Member takes

Implication

Key Points

Cite This Study

Also Consider

Also Consider