Liver fibrosis to cancer: scientists map path to block deadly transition

Over 80% of hepatocellular carcinoma (HCC) – the third-leading cause of cancer deaths globally – emerges from advanced liver fibrosis or cirrhosis. A comprehensive review in Hepatology International synthesizes decades of research to reveal how scarred liver tissue becomes a breeding ground for cancer.

The study identifies hepatic stellate cells (HSCs) as central villains. When activated by chronic injury (e.g., hepatitis, alcohol abuse), these cells deposit stiff scar tissue and secrete molecules that:

1. Fuel tumor growth (e.g., VEGF, Ang-1)

2. Suppress immune surveillance (e.g., via PD-L1)

3. Transform into cancer-associated fibroblasts (CAFs) that further accelerate malignancy.

Simultaneously, dysregulated signaling pathways (TGF-β‑Smad, NF-κB, Wnt), ECM remodeling, mitochondrial damage, epigenetic changes, and changes in the immune microenvironment remodel the liver into a pro-tumor environment. "This fibrosis-to-cancer axis isn't inevitable," stresses co-author Dr. Peng Luo of Southern Medical University. "By targeting key mechanisms – like HSC activation or immune evasion – we can intercept progression before malignancy takes hold."

Promising interventions include: 

- Liquid biopsies detecting tumor DNA/exosomes for early diagnosis.

- CAF-targeting therapies (e.g., FAP inhibitors, CAR-T cells) to disrupt tumor-supportive niches.

- Combination therapies blocking fibrosis drivers while enhancing immunity (immune checkpoint inhibitors).

The team emphasizes urgency: "Reversing fibrosis is possible, but once HCC develops, prognosis plummets. Our findings spotlight actionable checkpoints to prevent this transition."

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