Propranolol: Repurposing an old drug to modulate tumor growth, angiogenesis, and immunity in hepatocellular carcinoma

Abstract

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) are the key risk determinants for hepatocellular carcinoma (HCC), which is a significant public health issue worldwide. Molecular mechanisms of HBV- and HCV-related hepatocarcinogenesis are reviewed here, together with the therapeutic potential of propranolol against HCC. HBV and HCV promote HCC development through chronic inflammation, oxidative stress, and dysregulation of signaling pathways involved in proliferation, apoptosis, and immunity. Propranolol demonstrates promise in inhibiting tumor growth, angiogenesis, and metastasis in HCC by modulating adrenergic receptors and the immune response. Evidence suggests propranolol reduces inflammatory cytokines, enhances natural killer cell activity, and decreases the expression of immune checkpoint proteins such as programmed cell death protein 1 and T cell immunoglobulin and mucin domain-containing protein-3 in HCC cells. Clinical studies indicate that propranolol may lower HCC incidence and improve survival in cirrhotic patients. However, optimal dosing, long-term safety, and efficacy require further research through large randomized controlled trials. Aim: This paper aims to review the potential of propranolol as an adjuvant therapy for HBV/HCV-induced HCC by examining its antitumor, anti-angiogenic, and immunomodulatory effects. Conclusion: Propranolol represents a prospective adjuvant therapy for HBV/HCV-induced HCC that warrants continued investigation to fully elucidate its therapeutic potential against this disease. Relevance for patients: Propranolol may improve outcomes in HBV/HCV-related HCC by reducing tumor growth, angiogenesis, and immune evasion, offering a potential adjunct therapy to enhance patient survival and prognosis.

Keywords

Hepatocellular carcinoma / Hepatitis B virus / Hepatitis C virus / Propranolol / Cirrhosis

Funding

None.

Conflict of interest

The authors declare that they have no conflicts of interest.

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