The research team, led by Professor Carmen Wong Chak-lui (second left), has discovered a novel therapeutic application for atorvastatin, a widely used cholesterol-lowering drug, which could become a powerful new weapon in the fight against liver cancer.
A research team from the Department of Pathology at the University of Hong Kong's LKS Faculty of Medicine (HKUMed) has made a major breakthrough by discovering that atorvastatin, a widely used cholesterol-lowering drug could become a powerful new weapon in the fight against liver cancer. The findings demonstrate how this safe, affordable medication can exploit a hidden weakness in liver cancer cells and boosting the effectiveness of current treatments. This research was published on the Journal of Hepatology [link to publication].
Liver cancer is one of the deadliest cancers worldwide and is often diagnosed at an advanced stage when surgery is no longer an option. Current treatments such as targeted drugs and immunotherapy have limited success, providing only temporary relief for some patients. For patients with advanced liver cancer, especially those with metabolic dysfunction-associated steatotic liver disease (MASLD, formerly known as NAFLD) which is caused by high fat diet, treatment options are limited and outcomes are poor. Therefore, improving the therapeutic approaches has become a top priority.
Repurposing a cholesterol-lowering drug to fight liver cancer
The research team at HKUMed has uncovered a novel therapeutic application for atorvastatin, which is a common medication taken by millions of people to manage high cholesterol. The team demonstrated for the first time that atorvastatin can directly attack liver cancer cells by blocking the 'mevalonate pathway', a metabolic route crucial for cancer cell survival. This pathway is especially active in liver cancers associated with fatty liver disease, making this discovery highly relevant to this growing patient population.
'Liver cancer cells are adept at surviving by using various escape routes,' explained Professor Carmen Wong Chak-Lui from the Department of Pathology at the School of Clinical Medicine, HKUMed, who led the study. 'We found that these tumour cells rely on the mevalonate pathway to shield themselves from programmed cell death. By blocking this pathway with atorvastatin, we can effectively remove one of their key defences.'
Enhancing treatment effectiveness by combining atorvastatin with existing therapies
More excitingly, the research team found that combining atorvastatin with existing liver cancer treatments, such as the targeted therapy lenvatinib or immunotherapy drugs (anti-PD-1), markedly improves their efficacy, even in MASLD-associated hepatocellular carcinoma (MASLD-HCC). Laboratory models revealed atorvastatin alone reduced tumour growth by 33%. Remarkably, the combination of atorvastatin with anti-PD-1 therapy reduced tumour weight by nearly half (45%), while the combination with lenvatinib led to a 58% reduction.
'This approach could be a game-changer, especially for patients with fatty liver-associated liver cancer, which is becoming increasingly common worldwide,' said Professor Wong. 'Since atorvastatin is already widely used and well-tolerated, our study reveals the novel therapeutic potential for atorvastatin, repositioning it beyond its conventional role in cardiovascular health. It also offers a practical and accessible new way to strengthen current treatments and potentially improve survival outcomes for those with advanced liver cancer.'
Moving towards clinical trials to bring new hope to patients
The research team is planning to validate these findngs in clinical trials, aiming to provide this promising therapy to patients as soon as possible. If successful, this approach could offer new hope to those facing one of the most challenging cancers by repurposing a familiar and affordable medication in a brand-new way.
About the research team
The study was led by Professor Carmen Wong Chak-lui from the Department of Pathology, School of Clinical Medicine, HKUMed. The first author is Dr Chen Yiling. Major collaborators include Professor Wong Chun-ming, Professor Irene Ng Oi-lin and Professor Regina Lo Cheuk-lam from the same department.
Acknowledgements
This study was mainly supported by the Health and Medical Research Fund.
