HKU Researchers Discover Atorvastatin's Potential as Novel Liver Cancer Treatment
核心洞察
Researchers at the University of Hong Kong have discovered that atorvastatin, a widely used cholesterol-lowering drug, can directly attack liver cancer cells by blocking the mevalonate pathway crucial for cancer cell survival.
The study demonstrates that atorvastatin alone reduced tumor growth by 33%, while combinations with existing therapies achieved even greater reductions of 45-58% in laboratory models.
This breakthrough is particularly significant for patients with metabolic dysfunction-associated steatotic liver disease (MASLD)-related liver cancer, offering a safe and affordable treatment option.
A research team from the University of Hong Kong's LKS Faculty of Medicine has made a groundbreaking discovery that could transform liver cancer treatment by repurposing atorvastatin, a commonly prescribed cholesterol medication. The findings, published in the Journal of Hepatology, reveal how this affordable and well-tolerated drug can exploit a critical vulnerability in liver cancer cells while enhancing the effectiveness of existing therapies.
Targeting a Critical Cancer Pathway
The HKUMed research team demonstrated for the first time that atorvastatin can directly attack liver cancer cells by blocking the mevalonate pathway, a metabolic route essential for cancer cell survival. This pathway is particularly active in liver cancers associated with fatty liver disease, making the discovery highly relevant to a 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 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."
Significant Treatment Enhancement Through Combination Therapy
The research revealed particularly promising results when atorvastatin was combined with existing liver cancer treatments. Laboratory models showed that atorvastatin alone reduced tumor growth by 33%. However, the combination approaches yielded even more dramatic results: atorvastatin combined with anti-PD-1 immunotherapy reduced tumor weight by 45%, while the combination with lenvatinib, a targeted therapy, achieved a 58% reduction.
These findings are especially significant for patients with metabolic dysfunction-associated steatotic liver disease (MASLD)-associated hepatocellular carcinoma, formerly known as NAFLD-related liver cancer. This patient population faces particularly limited treatment options and poor outcomes with current therapies.
Addressing Critical Unmet Medical Need
Liver cancer represents one of the deadliest cancers worldwide, often diagnosed at advanced stages when surgical intervention is no longer viable. Current treatments, including targeted drugs and immunotherapy, provide only temporary relief for some patients and have limited success rates. For patients with advanced liver cancer, particularly those with MASLD caused by high-fat diets, treatment options remain severely limited.
"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."
Clinical Translation on the Horizon
The research team is now planning to validate these findings in clinical trials, aiming to bring this promising therapy to patients as quickly as possible. The approach offers several advantages: atorvastatin is already approved, widely available, and has an established safety profile from decades of use in cardiovascular medicine.
"It also offers a practical and accessible new way to strengthen current treatments and potentially improve survival outcomes for those with advanced liver cancer," Professor Wong noted. If successful in clinical trials, this approach could provide new hope for patients facing one of the most challenging cancers by repurposing a familiar and affordable medication in an entirely new therapeutic context.
The study was led by Professor Carmen Wong Chak-lui from the Department of Pathology, with Dr. Chen Yiling as the first author. Major collaborators included Professor Wong Chun-ming, Professor Irene Ng Oi-lin, and Professor Regina Lo Cheuk-lam from the same department. The research was primarily supported by the Health and Medical Research Fund.