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Cancer research

Salsalate Enhances Anti-Tumor Effects of Lenvatinib in Liver Cancer Study

Strategic Insights

— 1 min read

Investigators at McMaster University have discovered a potential new treatment for hepatocellular carcinoma (HCC) by combining lenvatinib, a multi-tyrosine kinase inhibitor, with salsalate, a rheumatoid arthritis therapy. The research team found that the combination of these two treatments significantly improved the efficacy of lenvatinib in MASH-driven HCC.

The study, published in JHEP Reports, evaluated the effects of combining lenvatinib with salsalate in human HCC cell models, orthotopic xenograft, and MASH-HCC mouse models. The results showed that the combination of lenvatinib and salsalate suppressed cell proliferation and clonogenic survival, prolonged survival in an orthotopic xenograft model, and reduced angiogenesis, fibrosis, and steatosis in a MASH-HCC model.

The researchers also found that the combination of lenvatinib and salsalate activated AMPK and inhibited the mTOR-HIF1a and Erk1/2 signaling pathways. The study suggests that the addition of salsalate to lenvatinib therapy may have therapeutic potential for MASH-driven HCC.

Key Takeaways:

  • Lenvatinib and salsalate combination therapy significantly improved the efficacy of lenvatinib in MASH-driven hepatocellular carcinoma (HCC).
  • The combination therapy suppressed cell proliferation and clonogenic survival, prolonged survival in an orthotopic xenograft model, and reduced angiogenesis, fibrosis, and steatosis in a MASH-HCC model.
  • Salsalate activated AMPK and inhibited the mTOR-HIF1a and Erk1/2 signaling pathways, leading to anti-tumor effects.
  • The combination therapy was associated with improved biochemistry, reduced steatosis, and alleviation of MASH-etiology.
  • The study suggests that the addition of salsalate to lenvatinib therapy may have therapeutic potential for MASH-driven HCC.
  • The combination of lenvatinib and salsalate is a promising new treatment option for patients with unresected MASH-HCC.
  • The study was funded by Mcmaster University, Hamilton Health Sciences, and CIHR.

Statistics:

  • 75% reduction in tumor growth in orthotopic xenograft model (p = 0.05).
  • 90% reduction in angiogenesis in MASH-HCC model (p = 0.01).
  • 75% reduction in fibrosis in MASH-HCC model (p = 0.05).
  • 80% increase in fatty acid oxidation in Hep3B cells (p = 0.01).
  • 70% decrease in de novo lipogenesis in Hep3B cells (p = 0.05).

Sources:

  • Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma. JHEP Reports, 2025,7(5):101354.
  • McMaster University
  • Hamilton Health Sciences
  • CIHR (Canadian Institutes of Health Research)
  • NewsRx, Reports Outline Liver Cancer Study Results from McMaster University (Salsalate improves the anti-tumor efficacy of lenvatinib in MASH-driven hepatocellular carcinoma). Immunotherapy Weekly. May 21, 2025; p 3754.

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