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Journal of Clinical and
Translational Research Propranolol as a treatment for HCC

Table 1. Summarized clinical trials of propranolol therapy for hepatocellular carcinoma
No. NCT number Study status Interventions Characteristics Population Years Country/
Region
1 NCT01298284 Unknown Propranolol Interventional/Phase IV No.: 60 2009 – 2011 Taiwan
Age: 18 – 80 years region
2 NCT01451658 Unknown Propranolol Interventional/Phase IV No.: 100 2009 – 2020 Taiwan
Age: 18 – 80 years region
3 NCT01970748 Recruiting Propranolol Interventional/Phase IV No.: 200 2009 – 2025 Taiwan
Age: 20 – 80 years region
4 NCT05451043 Not yet recruiting Propranolol/Cisplatin/ Interventional/Phase II No.: 62 2023 – 2028 Canada
Durvalumab/Tremelimumab Age: 18 – 80 years
Gemcitabine/Nab-paclitaxel
Abbreviations: HCC: Hepatocellular carcinoma; NCT: National Clinical Trial.

thus corresponding to a virological cure, have completely By activating AMP-activated protein kinase and
changed the therapy landscape for chronic HCV infection. blocking the mammalian target of the rapamycin pathway,
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Reaching SVR lowers the chance of developing HCC by metformin, a medication often used to treat type 2 diabetes,
dramatically reducing hepatic inflammation and stopping has also shown chemopreventive promise against HCC
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the growth of fibrosis. Studies have shown that compared by reducing the development and proliferation of tumor
to individuals with an active infection, those who achieve cells. It also lowers levels of insulin and insulin-like
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SVR had a much-decreased risk of HCC. Liver stiffness growth factor, both of which are linked to the development
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decreased from 12.3 kPa at baseline to 6.6 kPa over 5 years, of hepatocarcinogenesis. Although lactic acidosis in
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with the most significant improvement occurring in the individuals with renal impairment highlights the need for
1 year post-treatment. Early concerns about increased careful patient selection, clinical data indicates that diabetic
st
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HCC incidence and recurrence following DAA-induced patients treated with metformin have a much lower risk
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SVR, potentially due to disrupted immune surveillance, of HCC. Similarly, glucagon-like peptide-1 (GLP-1)
have been alleviated by recent meta-analyses, which found agonists decrease the risk of HCC by improving insulin
no evidence of differential HCC risk between DAA and sensitivity, reducing hyperinsulinemia, and exhibiting
IFN-based therapies. 62 anti-inflammatory qualities. A large cohort study by
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In addition to antiviral therapies, pharmacological Wang et al. found that GLP-1 agonists were associated
interventions offer promising strategies for HCC with a markedly reduced HCC risk compared to other
prevention, particularly in populations with chronic liver antidiabetic therapies, though gastrointestinal disturbances
disease, metabolic dysfunction, or other risk factors. and pancreatitis risks warrant careful monitoring.
Aspirin, for instance, demonstrates chemopreventive effects By enhancing indicators of steatosis and fibrosis,
through the inhibition of cyclooxygenase-2, reducing pro- sodium-glucose cotransporter 2 inhibitors, which are
inflammatory prostaglandins and disrupting platelet– mainly used for glycemic management, have the potential
tumor cell interactions that facilitate tumor growth and to prevent HCC. Angiotensin receptor blockers and
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metastasis. Meta-analyses consistently show that regular angiotensin-converting enzyme inhibitors have anti-
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aspirin use lowers HCC risk, particularly in individuals inflammatory and anti-fibrotic effects, which lessen liver
with chronic liver disease, though gastrointestinal fibrosis, a significant risk factor for HCC. Known for its
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bleeding and hemorrhagic stroke risks necessitate immunomodulatory and anti-inflammatory properties,
careful risk–benefit assessments. 64,65 By inhibiting Vitamin D supplements have also been associated with
hydroxymethylglutaryl-CoA reductase, statins reduce a lower risk of HCC, with a deficit markedly raising the
oncogenic signaling pathways such as Ras/Raf/MEK/ risk of liver cancer. Finally, nutraceuticals and herbal
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ERK and modify the mevalonate pathway, which has anti- supplements, including curcumin, resveratrol, and
inflammatory, immunomodulatory, and antiproliferative silymarin, have shown promise in preclinical studies
effects. Although myopathy or rhabdomyolysis is still due to their antioxidant, anti-inflammatory, and anti-
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a problem, especially in patients with decompensated proliferative properties. However, cases of drug-
cirrhosis, lipophilic statins, such as simvastatin and induced liver injury and variability in quality and potency
atorvastatin, have stronger protective benefits against HCC highlight the need for regulation and standardization.
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than hydrophilic versions. 67 Collectively, these pharmacological interventions offer

Volume 11 Issue 4 (2025) 24 doi: 10.36922/JCTR025080010