Liver cancer remains one of the most lethal forms of cancer globally, with cases linked to metabolic dysfunction on the rise. A research team from The Hong Kong Polytechnic University (PolyU) has made a significant advancement by developing a novel antibody that targets a fat cell protein known to promote cancer growth. This breakthrough, published in the Journal of Clinical Investigation, could pave the way for new treatment options for liver cancer patients.
The study, led by Prof. Terence LEE, Associate Head and Professor in the Department of Applied Biology and Chemical Technology at PolyU, identified the protein fatty acid-binding protein 4 (FABP4) as a critical factor in accelerating tumour growth. The research highlights how metabolic dysfunction-associated steatotic liver disease (MASLD), commonly referred to as fatty liver disease, affects approximately one in four individuals worldwide and significantly increases the risk of developing liver cancer.
In patients suffering from MASLD, fat cells contribute to insulin resistance and chronic inflammation, leading to fat accumulation in the liver. This can severely compromise liver function and potentially result in cancer. Current treatment options for MASLD-induced liver cancer are limited, and the effectiveness of existing immunotherapies remains insufficient.
Through advanced mass spectrometry techniques, Prof. Lee’s team discovered that patients with MASLD-induced liver cancer exhibited markedly elevated levels of FABP4 in their serum. Further investigations revealed that FABP4 activates various pro-proliferative signalling pathways within cells, prompting cancer cells to proliferate at an accelerated rate.
The team has successfully engineered a monoclonal antibody capable of neutralising FABP4. This antibody not only inhibits the growth of cancer stem cells driven by FABP4 but also enhances the immune system’s ability to target and destroy cancer cells. Prof. Lee remarked, “This neutralising antibody against FABP4 demonstrates significant potential in inhibiting tumour growth and activating immune cells, providing a complementary approach to current immunotherapy strategies.”
He further emphasized that understanding how adipocyte-derived FABP4 influences liver cancer cells elucidates the disease mechanisms, particularly in obese patients. By intervening in the relevant signalling pathways, researchers could develop effective strategies to combat this aggressive cancer.
The ongoing research is backed by the Innovation and Technology Fund of the Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region of the People’s Republic of China. PolyU has filed a non-provisional patent for the developed antibody, actively working to enhance its binding affinity to support future clinical applications.
Prof. Lee expressed optimism regarding the potential of this adipocyte-targeted immunotherapy, stating, “If its efficacy can be proven in clinical trials, it could offer new hope to many affected individuals.” As the research progresses, it holds promise for expanding treatment options for those suffering from MASLD and related liver cancer, addressing a crucial area of unmet medical need.
