Inhibition of eIF4E signaling by ribavirin selectively targets lung cancer and angiogenesis

Area of Science:

• Oncology
• Pharmacology
• Molecular Biology

Background:

• Lung cancer remains a significant therapeutic challenge despite advances in immunotherapy and targeted therapy.
• There is a critical need for novel therapeutic strategies to improve lung cancer treatment outcomes.

Purpose of the Study:

• To investigate the potential of ribavirin, an existing antiviral drug, as a novel therapeutic agent for lung cancer.
• To evaluate ribavirin's efficacy, toxicity, synergistic effects, and mechanism of action in lung cancer models.

Main Methods:

• Testing ribavirin's activity against diverse lung cancer cell lines.
• Assessing ribavirin's efficacy and toxicity in a lung xenograft mouse model.
• Investigating ribavirin's anti-angiogenic properties by examining its effect on human lung tumor-associated endothelial cells (HLT-EC).
• Elucidating the molecular mechanism of ribavirin action through signaling pathway analysis.

Main Results:

• Ribavirin demonstrated broad activity against various lung cancer cell lines at clinically achievable concentrations with minimal toxicity to normal cells.
• Ribavirin exhibited synergistic effects with paclitaxel and showed potent efficacy and reduced toxicity in vivo.
• Ribavirin inhibited angiogenesis by suppressing capillary network formation, growth, and survival of HLT-ECs.
• Mechanism studies revealed that ribavirin suppresses eIF4E and mTOR signaling, inhibiting protein translation in lung cancer cells.

Conclusions:

• Ribavirin is a promising candidate for lung cancer treatment due to its dual action on tumor cells and angiogenesis.
• Ribavirin offers advantages over existing agents by targeting both cancer cell proliferation and tumor vascularization.
• The findings support further investigation of ribavirin as a potential repurposed drug for lung cancer therapy.