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Programme in Translational and Clinical Liver Research

​Research head:​Professor Pierce CHOW
​Research team:

Lynette LAI

​Dr Sin Chi CHEW

Dr Lingyan WU

Dr Ah Jung JEON

Xiao Quan ONG

Wen Huan LING

Fiona Ni Ni MOE

Jacelyn CHUA

Weng Yan NG

Jade Goh

Rachel CHOI

Angelina LOO

Yuki SIM

Primary liver cancer or hepatocellular carcinoma (HCC) imposes significant challenges to healthcare with huge unmet clinical needs. HCC is the second leading cause of cancer-related mortality worldwide in males and 80% of HCC are found in the Asia-Pacific. While early-stage HCC is potentially curable by surgical resection, liver transplantation or radiofrequency ablation, recurrences remain common and limits overall survival. Survival in intermediate stage HCC may be prolonged by loco-regional therapy in advanced HCC by systemic therapies. Overall, clinical outcomes in HCC remain poorer than that of other common cancers due to the lack of efficacious systemic therapies. The biology of HCC is intrinsically challenging as HCC is the common end-point of a number of etiologies with different molecular pathways. In addition, significant heterogeneity also exists within the same tumor.

Concerted research leveraging on an inter-disciplinary approach is therefore required to address these challenges. The Program in Translational and Clinical Liver Cancer Research, lead by Prof Pierce Chow, is a multi-institutional and multi-national enterprise with NCCS leading translational research platforms and prospective clinical studies in HCC. Nested within the program is the Secretariat of the Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group (17 countries, >50 sites) which in Q4 2020 will coordinate the enrolment of 2,000 patients at risk for HCC and a parallel cohort of 100 HCC patients across 6 specialist centers and 8 polyclinics in Singapore (AHCC10). Another new initiative is an investigator-initiated multi-national randomized phase II trial spanning sites in the Asia-Pacific (Singapore, China, South Korea and Taiwan) planned to commence in 2021 (AHCC09). Other active studies under the AHCC Trials Group include a real world data Asia-Pacific HCC Registry (AHCC08) and a prospective multi-omics study on a surgically resected HCC cohort (AHCC07). Our current portfolio of clinical studies and translational research platforms include:

• Early detection of hepatocellular carcinoma (HCC): miRNA, microbiome and imaging biomarkers in the evolution of chronic liver disease in a high-risk prospective cohort (AHCC10). Investigator-initiated multi-center study in collaboration with clinical sites (CGH, NCCS, NUH, SGH, SKH, TTSH, SingHealth Polyclinics), academic institutes (NTU, Duke-NUS) and industrial partners (MiRXES Pte Ltd, Perspectum Asia Pte Ltd,  Asian Microbiome Library Pte Ltd) supported by A*Star Industry Alignment Fund – Industry Collaboration Project (IAF-ICP) Grant.

• Hepatocellular Carcinoma Registry in Asia (AHCC08). Investigator-initiated multi-national clinical study in collaboration with IQVIA.

 Precision Medicine in Liver Cancer across an Asia-Pacific Network (AHCC07) – the PLANET study. Investigator-initiated multi-omics multi-national prospective cohort study in collaboration with clinical sites (NCCS, SGH, NUH, University Malaya Medical Centre - Malaysia, The Medical City – Philippines, National Cancer Institute – Thailand, Duke University Hospital – USA) and academic institutes (GIS, IMCB, TII, NTU, NUS)  supported by NMRC Translational and Clinical Research Grant.

• Decoding global gene expression in Liver Cancer through Deep Learning and standard-of-care Clinical Imaging. Translational Research study in collaboration with A*STAR I2R supported by Innovation to Startup Grant.

• Comprehensive interrogation of the epigenetics promoter and enhancer landscape in HCC to identify aberrant regulatory mechanisms associated with HCC. Translational Research study in collaboration with A*STAR GIS supported by NMRC Clinician-Scientist Individual Research Grant (CS-IRG) Grant.

• A Prospective Study to develop a Genomics-Immunomics-Phenomics Platform for Precision Medicine in HCC. Translational Research study in collaboration with GIS, TII, and NTU supported by NMRC Clinician Scientist Award Grant.

• The use of LiverMultiScan in the analysis of MRI scans in HCC for improved monitoring of patients’ prognosis and selection of therapy. Investigator-initiated prospective clinical study in collaboration with Perspectum Diagnostics Pte Ld.

• Predicting survival after surgical resection for entire spectrum of anatomically resectable HCC: a Metro-ticket approach. Investigator-initiated clinical study in collaboration with Duke University Medical Center.

Selected publications:

  1. Ankur Sharma*, Justine Jia Wen Seow, Charles-Antoine Dutertre, Rhea Pai, Camille Blériot, Archita Mishra, Regina Men Men Wong, Gurmit Singh Naranjan Singh, Samydurai Sudhagar, Shabnam Khalilnezhad, Sergio Erdal, Hui Min Teo, Ahad Khalilnezhad, Svetoslav Chakarov, Tony Kiat Hon Lim, Alexander Chung Yaw Fui, Alfred Kow Wei Chieh, Cheow Peng Chung, Glenn Kunnath Bonney, Brian Goh Kim Poh, Jerry KY Chan8, Pierce Kah-Hoe Chow Hoe*, Florent Ginhoux*, Ramanuj DasGupta*. (2020). Onco-fetal reprograming of endothelial cells drivesimmunosuppressive macrophages in Hepatocellular Carcinoma. Cell. doi: 10.1016/j.cell.2020.08.040
  2. Chow, P.K.H., Gandhi, M., Tan, S.B., Asia-Pacific Hepatocellular Carcinoma Trials, G., et al. (2018). Sirvenib: Selective Internal Radiation Therapy Versus Sorafenib in Aisa-Pacific Patients with Hepatocellular Carcinoma. J Clin Oncol 36, 1913-1921.10.1200/JCO.2017.76.0892 
  3. Lim C.J., Chow, P.K.H., Albani, S., Chew, V., et al. (2018). Multidimensional Analyses Reveal Distinct Immune Microenvironment in Hepatitis B Virus-Related Hepatocellular Carcinoma. Gut. 10.1136/gutjnl-2018-316510. 
  4. Chew V., Albani, S., Chow, P.K.H., et al. (2018). Immune Activation Underlies a Sustained Clinical Response to Yttrium-90 Radioembolization in Hepatocellular Carcinoma. Gut. 10.1136/gutjnl-2017-315485 
  5. Zhai, W., Foo, R.S., Chow, P.K.H., et al. (2017). The Spatial Organization of Intra-Tumour Heterogeneity and Evolutionary Trajectories of Metastases in Hepatocellular Carcinoma. Nat Comm 8, 4565. 10.1038/ncomms14565. 
  6. Chew V., Albani, S., Chow, P.K.H., et al. (2017). Delineation of an Immunosuppressive Gradient in Hepatocellular Carcinoma using High-Dimensional Proteomic and Transcriptomic Analyses. Proc Natl Acad Sci USA 114, E5900-E5909. 10.1073/pnas.1706559114.