HKU Identifies Key Protein AGPAT4 in Liver Cancer Drug Resistance, Develops Inhibitor to Prevent Recurrence

                           HKU Identifies Key Protein AGPAT4 in Liver Cancer Drug Resistance, Develops Inhibitor to Prevent Recurrence

China News Service, Hong Kong (Reported by Han Xingtong, August 12) ; The University of Hong Kong (HKU)

The University of Hong Kong (HKU) announced on August 12 that its research team has identified AGPAT4, a key protein linked to drug resistance in liver cancer, and developed a new small-molecule inhibitor CL26. This inhibitor, when combined with sorafenib, significantly suppresses tumor growth, improves treatment outcomes, and shows potential in preventing cancer recurrence with low side effects.

内容

Hepatocellular carcinoma, the most common type of liver cancer, is often characterized by drug resistance and high recurrence rates. Cancer cells in hepatocellular carcinoma promote tumor growth by significantly altering metabolic processes, which has long been a challenge in treatment.

A research team from the School of Biomedical Sciences at HKU's Faculty of Medicine, co-led by Professor Ma Kwai-yee and Assistant Professor Zhong Yichen, made a breakthrough in this area. They found that a specific metabolic pathway helps cancer cells maintain their stemness—the ability to grow, spread, and survive. This pathway involves the protein AGPAT4, which is highly expressed in embryonic stem cells and hepatocellular carcinoma cells but rarely found in normal tissues.

Professor Ma Kwai-yee explained that AGPAT4 acts like a switch, enhancing the flexibility and aggressiveness of cancer cells. Experiments on mice showed that blocking AGPAT4 can slow down tumor growth and improve the efficacy of sorafenib, a commonly used targeted drug for liver cancer.

Building on this discovery, the team developed CL26, a compound specifically targeting AGPAT4. In patient tumor models, the combination of CL26 and sorafenib significantly inhibited tumor proliferation. Importantly, toxicological evaluations indicated that CL26 has low side effects, suggesting its potential for safe application in clinical treatment.

Assistant Professor Zhong Yichen noted that the research team is currently conducting larger-scale preclinical studies to further evaluate the efficacy and safety of CL26, with the goal of advancing it to new drug research and clinical trial stages. This development holds promise for improving the prognosis of liver cancer patients by addressing drug resistance and reducing recurrence risks.