HKU's World-First 'Liver-in-Cube' Revolutionises Liver Cancer Treatment with Precision

Liver cancer is the sixth most common cancer worldwide and the third leading cause of cancer-related deaths. A recent report published in 'The Lancet' predicts that the number of new liver cancer cases will increase from 870,000 in 2022 to 1.52 million by 2050, nearly doubling the figure. If the current trend continues, this increase could result in 1.37 million deaths.

Traditional cancer therapies often overlook patient-specific and dynamic tumor immune environments, causing ineffective treatments, toxic side effects, and critical delays. The University of Hong Kong (HKU) has developed 'Liver-in-Cube', the world's first 3D-bioprinted platform that precisely reconstructs the liver cancer microenvironment in the lab using a patient's own cells and extracellular matrix. This platform offers a fast and reliable service to help patients identify the most effective personalised treatments and pave the way for a standardised, high-throughput solution for drug assessment and development.

The invention can accurately simulate tumour characteristics of individual patients, such as the cell numbers, tissue stiffness and immune microenvironments, enabling doctors to swiftly assess the efficacy and side effects of various drugs and emerging therapies, leading to more precise treatment decision. This technology has received the ‘Gold Medal’ at the International Exhibition of Inventions of Geneva, ‘Special Grand Prize’ at Prize of the China Invention Association, and ‘Best-Performing Start-Up Award’at Asia Summit on Global Health (ASGC) Conference.

The technology has received the ‘Gold Medal’ at the International Exhibition of Inventions of Geneva, ‘Special Grand Prize’ at Prize of the China Invention Association, and ‘Best-Performing Start-Up Award’at Asia Summit on Global Health (ASGC)Conference. Photo source: HKUMed

From ‘Trials to Tailored Treatment’: Seizing the Golden Treatment Window

Currently, there is a lack of personalised drug-screening platforms for liver cancer treatment in the market, which often makes patients undergo multiple treatment failures in the search for the most suitable drug. This not only imposes a heavy financial burden but may also delay the timing in killing the tumour cells effectively. The 'Liver-in-Cube' directly addresses this pain point by accelerating the evaluation of the efficacy and side effects of various drugs for patients, allowing doctors to identify the optimal treatment method for patients and reducing the risk of cancer recurrence due to treatment delays. The ‘Liver-in-Cube' has now started patient recruitment at local hospitals to expedite clinical trials and advance its transition into clinical application.

The 'Liver-in-Cube' developed by HKU, Photo source: HKUMed

Dual Value in Clinical and Research Excellence

Professor Man Kwan, Chair Professor in the Department of Surgery, School of Clinical Medicine, HKUMed, who led the research project, stated that ‘Liver-in-Cube' can speed up the identification of the most effective drugs for patients, significantly enhancing treatment efficiency and reducing side effects, with the potential to greatly improve patient survival rates. In pharmaceutical development, the technology serves as a substitute for animal models, accelerating preclinical efficacy and safety testing for new drugs with more accurate data to increase the success rate of further clinical trials. This invention can shorten the new drug development cycle with reducing costs. In the field of basic research, the model assists researchers in exploring immune regulation mechanisms and discovering new therapeutic targets and strategies. The application prospects of the ‘Liver-in-Cube' are extensive, and its technological framework can be expanded to other liver diseases and cancers, promoting the widespread adoption of precision medicine. Currently, the technology is undergoing clinical trials in local public and private hospitals. The team aims to leverage the scientific data to facilitate the commercialisation of the technology and make it available in both local and overseas markets, thus benefitting a wide range of patients.

The University of Hong Kong (HKU) has developed‘Liver-in-Cube’,the world’s frst 3D-bioprinted platform that precisely reconstructs the liver cancer microenvironment in the lab using a patient’s own cells and extracellular matrix. Photo source: HKUMed

Five core technologies of ‘Liver-in-Cube':

• 1. Novel Technology for Cell and Matrix Protein Separation: Simultaneously extracts hepatocytes, tumor cells, immune cells, and matrix proteins from the tissue of the liver cancer patient, accurately simulating individual tumor characteristics.

• 2. Advanced 3D Bioprinting: Creates a biomimetic model incorporating normal tissue, tumor tissue, and vascular structures, surpassing traditional 3D cell culture and organoid products in reproducing a patient's tumor architecture.

• 3. AI-assisted patient parameterisation and printing: Utilising AI models trained on clinical biobanks, we correlate pathological features, tissue stiffness, and tumor immune microenvironment subtypes to determine the optimal geometric structure and bio-ink composition for each patient.

• 4. Customised patient-specific tumor characterisation system: By precisely measuring patient-specific parameters such as tumor stiffness and immune profiles, we reconstruct a highly biomimetic, individualized tumor microenvironment for each patient.

• 5. Innovative Tumor Model with Microvascular System: Enables continuous drug testing and evaluation of various therapies, enhancing the assessment of treatment effects in a laboratory setting.

Led by Professor Man Kwan from the Department of Surgery, HKUMed, the research
team focuses in the study of postoperative recurrence and immune microenvironment
of liver cancer. Over the decades, the team has become internationally recognised as
the leading force in the fields of liver oncology, transplant oncology, and transplant
immunology.

A recent study led by the Department of Medicine, School of Clinical Medicine, LKS Faculty of Medicine of the University of Hong Kong (HKUMed), in collaboration with the University of Hong Kong-Shenzhen Hospital, has demonstrated that combining an innovative coronary imaging technology known as the caFFR system, with diabetes drug SGLT2 inhibitors can significantly reduce the risks of major adverse cardiovascular events (MACE), heart failure and death among patients with type 2 diabetes mellitus (T2DM) and coronary artery disease. This dual-pronged strategy provides a precise measurement of coronary blood flow while lowering glucose levels, offering an effective approach to treating exceptionally high-risk patients. The findings were published in the Diabetes and Metabolism Journal link to the publication.

caFFR images access coronary blood flow

Patients with T2DM commonly develop more complex and severe forms of coronary artery disease, often involving multiple narrowed or blocked arteries. This complexity makes it challenging for cardiologists to achieve 'complete revascularisation', where all significantly blocked arteries are fully opened to restore blood flow. Without detailed functional assessment, some blockages that appear mild on imaging but are functionally important may be overlooked. If these high-risk blockages are not identified, patients may be at risk of 'incomplete revascularisation' and experience persistent ischaemia despite treatment, ultimately increasing their long-term cardiac risk.

To address this challenge, Professor Yiu Kai-hang, Clinical Professor in the Department of Medicine, School of Clinical Medicine, HKUMed, led a research team to evaluate the use of the caFFR system, an innovative imaging technology that allows accurate measurement of coronary blood flow from standard angiogram images. This technique enables cardiologists to identify which arterial blockages are truly responsible for ischaemia, thus supporting more precise decision-making and the development of more effective interventional treatment strategies for high-risk patients.

Professor Yiu Kai-hang explains that the functional assessment using the caFFR system is crucial for achieving optimal revascularisation in diabetic patients. SGLT2 inhibitors offer robust cardiovascular protection and significantly improve survival outcomes, even in cases of incomplete revascularisation.

SGLT2 inhibitors provide powerful cardiac protection

The study analysed data from 671 patients with both T2DM and coronary artery disease who underwent angiogram imaging in public hospitals between 2014 and 2016. While complete revascularisation was achieved in some patients, many still had residual stenosis after undergoing the revascularisation procedure due to diffuse and complex diabetic atherosclerosis. Remarkably, for those with incomplete revascularisation, the use of SGLT2 inhibitors provided powerful vascular protecton. The three-year incidence of MACE was markedly reduced from 17.8% to 8.3%, while all-cause mortality dropped sharply from 16.3% to 6.3% over the same period.

HKUMed reveals that combining novel caFFR imaging technology with glucose lowering drug effectively protects the heart of diabetic patients. In the photo are Professor Yiu Kai-hang (left), who led the research, and his team member Dr Xuan Haochen.

'Our findings show that functional assessment using the caFFR system allows clinicians to accurately identify blockages that truly cause ischemia, which is crucial for achieving optimal revascularisation in diabetic patients,' said Professor Yiu Kai-hang. 'Moreover, even when complete revascularisation cannot be achieved, SGLT2 inhibitors offer robust cardiovascular protection, significantly improving survival outcomes. This dual approach represents a major step forward in managing heart disease among individuals with diabetes.'

The study underscores the complementary roles of precision interventional imaging and pharmacological therapy in improving outcomes for diabetic patients with coronary artery disease. By integrating caFFR-guided vascular reconstruction procedures with SGLT2 inhibitor therapy, clinicians can better tailor treatment to each patient's needs, offering both anatomical and metabolic protection for the heart.

Professor Yiu added, 'This study has importance implications for clinical practice. It demonstrates that even when structural risks in the blood vessels may persist, SGLT2 inhibitors provide a vital safety net, reducing future cardiovascular risks. The findings reinforce HKUMed's ongoing commitment to translating clinical innovation into better patient care.'

The study was led by Professor Yiu Kai-hang, Clinical Professor, Department of Medicine, School of Clinical Medicine, HKUMed, and conducted in collaboration with the University of Hong Kong–Shenzhen Hospital.