Exploring the scientific evidence for antiviral drug oseltamivir's unexpected potential against hepatocellular carcinoma
Liver cancer stands as one of the most formidable challenges in modern oncology. As a leading cause of cancer-related mortality worldwide, it claims hundreds of thousands of lives each year, with its incidence steadily rising. Hepatocellular carcinoma (HCC), which accounts for approximately 90% of all primary liver cancer cases, is particularly aggressive and often diagnosed at advanced stages when treatment options are limited 1 .
HCC accounts for approximately 90% of primary liver cancer cases and represents a significant global health challenge with limited treatment options at advanced stages.
The established safety profile and known pharmacokinetics of oseltamivir offer potential for accelerated clinical implementation compared to novel drug compounds.
Oseltamivir has long been recognized as a neuraminidase inhibitor, effectively preventing influenza viruses from replicating and spreading within the body. However, the discovery of its potential anti-cancer properties emerged from a fascinating scientific connection: the NEU1 enzyme, a specific type of neuraminidase found in human cells, appears to play a significant role in cancer progression 2 6 .
In 2021, a pivotal study conducted by Huang and colleagues provided the first systematic evidence of oseltamivir's activity against liver cancer 1 5 . This comprehensive investigation employed a multi-faceted approach to validate the drug's effects across various experimental models.
Researchers treated liver cancer cell lines (Huh-7 and HepG2) with varying concentrations of oseltamivir and measured cell survival using MTT assays 1 .
Wound healing assays and Transwell experiments examined oseltamivir's impact on cancer cell movement and invasion capabilities 1 .
Flow cytometry and immunoblotting techniques investigated whether oseltamivir triggered apoptosis, autophagy, or both in cancer cells 1 .
Xenograft animal models with human liver cancer cells were treated with oseltamivir to confirm effects in living organisms 1 .
| Cell Line | Primary Death Mechanism | Key Molecular Markers | Secondary Mechanisms |
|---|---|---|---|
| Huh-7 | Autophagy | ↑LC3-II/LC3-I ratio, ↑Beclin-1, ↓p62 | Minimal apoptosis |
| HepG2 | Apoptosis & Autophagy | ↑Apaf-1, ↑cleaved caspase-3, ↑cleaved PARP-1, ↑LC3-II/LC3-I | Combined pathway activation |
The investigation into oseltamivir's anti-cancer properties relies on a specific set of research tools and materials that enable precise evaluation of its effects on cancer cells.
Following the initial discovery of oseltamivir's anti-liver cancer activity, subsequent research has delved deeper into the molecular mechanisms behind these effects. A 2025 study published in Frontiers in Pharmacology provided crucial insights into how oseltamivir disrupts cancer cell function by targeting NEU1 and impacting lipid metabolism 2 6 .
"Oseltamivir, by inhibiting NEU1, promotes a process called lipophagy—a specific type of autophagy that breaks down lipid droplets within cells." 2
Disrupts signaling pathways that promote cancer aggressiveness
Depletes lipid resources that cancer cells depend on for survival
Liver cancer cells may be more sensitive to oseltamivir than to some conventional chemotherapeutic agents with potentially reduced drug resistance 2 .
When considering repurposing any drug, understanding its safety profile is paramount. Oseltamivir has been used for decades in influenza treatment, with generally favorable safety data. However, a 2025 analysis of the FDA Adverse Event Reporting System did identify hepatotoxicity (liver damage) as a potential concern 7 .
These findings highlight the importance of careful patient selection and monitoring if oseltamivir were to be deployed as a cancer therapeutic, particularly with regular liver function tests to detect any potential toxicity early.
The journey from laboratory discovery to clinical application is typically long and complex, and oseltamivir's potential repurposing for liver cancer treatment is still in its early stages. While the preclinical data from multiple studies is compelling, definitive clinical trials in human patients with liver cancer have not yet been conducted.
Definitive studies in human patients with liver cancer to establish efficacy and optimal dosing.
Identification of responsive tumor types based on molecular characteristics.
Potential to enhance effectiveness of other chemotherapy drugs in combination regimens.
The investigation into oseltamivir's potential against liver cancer represents a fascinating case study in scientific serendipity and drug repurposing. What began as a treatment for influenza has revealed unexpected potential against one of oncology's most challenging diseases. The compelling laboratory evidence, demonstrating multiple mechanisms of action including NEU1 inhibition and lipophagy induction, provides a solid foundation for further exploration.