Liver cancer ranks among the most lethal malignancies globally, with metabolic dysfunction-related forms rising sharply in incidence. A pioneering breakthrough from The Hong Kong Polytechnic University (PolyU) now offers a fresh therapeutic perspective. This innovative research pinpoints a specific protein secreted by adipocytes—fat cells—that accelerates tumor progression, and for the first time, introduces a monoclonal antibody capable of neutralizing this protein. The results, prominently featured in the Journal of Clinical Investigation, could fundamentally alter how metabolism-linked liver cancer is managed.
Metabolic dysfunction-associated steatotic liver disease (MASLD), previously referred to as non-alcoholic fatty liver disease (NAFLD), affects nearly 25% of the world’s population. MASLD is characterized by abnormal fat accumulation within the liver, often driven by systemic insulin resistance and chronic inflammatory states originating from dysfunctional adipose tissue. This diseased milieu establishes a fertile ground for hepatocarcinogenesis, yet current treatment protocols remain inadequate, with limited efficacy of existing immunotherapies against MASLD-induced hepatocellular carcinoma (HCC).
The research team, under the leadership of Professor Terence Lee, Associate Head of PolyU’s Department of Applied Biology and Chemical Technology, harnessed advanced proteomic methodologies, specifically mass spectrometry, to dissect the serum profiles of patients afflicted with MASLD-driven liver cancer. Their investigations uncovered a conspicuous elevation of fatty acid-binding protein 4 (FABP4), an adipocyte-derived lipid chaperone, correlating strongly with tumor aggressiveness and patient prognosis. FABP4’s role extends beyond mere lipid transport; it acts as a molecular orchestrator activating multiple oncogenic signaling cascades within hepatic cancer cells.
FABP4 facilitates tumor proliferation by potentiating key intracellular pathways involved in cell cycle regulation and survival, effectively pushing cancer cells into hyperactive replicative states. Furthermore, FABP4 signaling modulates the tumor microenvironment, dampening immune surveillance mechanisms and enabling neoplastic cells to evade immune destruction. This dual pro-cancer role establishes FABP4 as a compelling molecular target for therapeutic intervention in metabolic liver cancers.
In a landmark achievement, Prof. Lee’s team engineered a monoclonal antibody specifically designed to bind and neutralize FABP4. This biotherapeutic agent demonstrably inhibits the proliferative surge of FABP4-driven cancer stem cells—subpopulations notorious for chemoresistance and metastatic potential. Besides direct tumor suppression, the antibody enhances antitumor immunity by revitalizing the cytotoxic functions of immune effector cells within the tumor niche, suggesting a synergistic mechanism when used in combination with established immunotherapy modalities.
In vivo models of MASLD-induced liver cancer treated with the anti-FABP4 antibody exhibited significant tumor growth attenuation, compelling reductions in tumor volume, and improved survival metrics. These preclinical outcomes represent a vital proof-of-concept supporting FABP4 neutralization as a viable strategy to counteract metabolic liver cancer’s progression, which traditional therapies have lacked the precision to curtail effectively.
Professor Lee emphasized the antibody’s transformative potential: “Targeting adipocyte-derived FABP4 offers a dual mechanism—directly suppressing tumor expansion and concurrently unleashing immune attack capabilities—thereby complementing and enhancing existing therapeutics.” This highlights the growing recognition of the interplay between metabolic dysregulation, cancer biology, and immune modulation in liver cancer pathology.
Moreover, elucidating the mechanistic underpinnings of FABP4’s influence on cancer cells sheds light on the intercellular crosstalk between adipose tissue and the hepatic microenvironment. This insight deepens scientific understanding of how obesity and metabolic syndromes translate into oncogenic triggers, particularly in hepatocytes, and underscores the need for holistic approaches that integrate metabolic and immunological interventions.
As the research progresses into optimization phases, PolyU has secured intellectual property rights through a non-provisional patent application, focusing on enhancing the antibody’s binding affinity and pharmacokinetic profiles. These optimizations aim to maximize clinical efficacy and safety, setting the stage for eventual translation from bench to bedside.
If forthcoming clinical trials validate its effectiveness, this adipocyte-targeted immunotherapy could revolutionize treatment paradigms for MASLD patients who currently face limited options and poor prognoses. The approach exemplifies precision medicine by tailoring treatments to disease etiology rooted in metabolic imbalance and immune escape.
By opening a therapeutic avenue that bridges fat metabolism and immune modulation, this discovery from PolyU advances the frontier of oncology and metabolic disease intersection. It promises a future wherein liver cancer triggered by metabolic dysfunction might become more manageable, ultimately improving survival and quality of life for afflicted patients worldwide.
The study was financially supported by the Innovation and Technology Fund under the Innovation and Technology Commission of the Hong Kong Special Administrative Region government, reflecting robust institutional endorsement for cutting-edge biomedical research addressing critical global health challenges.
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News Publication Date: 4-Feb-2026
Web References: http://dx.doi.org/10.1172/JCI182322
References: Journal of Clinical Investigation
Image Credits: polyu
Keywords: Liver cancer, Antibody therapy, Proteins, Adipocytes, Metabolic disorders, Immune regulation
Tags: adipocyte protein in tumor progressionadvancements in liver cancer immunotherapychronic inflammation and liver cancerinnovative antibody therapy for liver cancerinsulin resistance and liver diseaseMASLD and hepatocellular carcinomametabolic dysfunction and liver cancermonoclonal antibodies in cancer therapynew approaches in metabolic liver cancer managementPolyU research on liver cancer treatmentproteomic methodologies in cancer researchtargeting fat cell proteins in cancer treatment
