Two surgeon-scientists receive top national research awards to improve outcomes for SG-prevalent liver and head & neck cancers

Singapore, 6 February 2025 – In a boost to research efforts aimed at tackling cancers prevalent in Asia, the Singapore Ministry of Health through the National Medical Research Council (NMRC) Office, MOH Holdings Ptd Ltd, has recently awarded STaR Investigator Awards to two surgeon-scientists at the National Cancer Centre Singapore (NCCS). The STaR Investigator Award is Singapore’s prestigious research award for clinician scientists, providing up to $6 million in support over five years to conduct translational and clinical research, health promotion, preventive health, population health and health services research, and/or health technology.

Professor Pierce Chow, Senior Consultant Surgeon, Division of Surgery and Surgical Oncology, Singapore General Hospital (SGH) and NCCS, received the STaR Investigator Award to investigate unrecognised causes of the primary liver cancer, hepatocellular carcinoma (HCC), with the aim of improving screening, diagnosis and treatment of the deadly disease.

Professor Gopal Iyer, Head and Senior Consultant, Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, SGH and NCCS, received the STaR Investigator Award to conduct clinical studies focused on treating head and neck cancers with immune cell therapeutics, with plans to develop a national resource to manufacture these therapies in Singapore.

Targeting liver cancer through the gut

Liver cancer: A pressing challenge in Asia

Hepatocellular carcinoma (HCC) has the highest mortality-to-incidence ratio of any solid tumour at 0.92,[1] meaning that diagnosis is almost synonymous with fatality. Poor outcomes are largely due to late diagnosis and limited understanding of the disease’s molecular biology, contributing to a lack of predictive biomarkers, in turn leading to less effective treatment options. HCC is especially prevalent in Asia, and presents a significant public health challenge in Singapore, where 2,753 new cases were diagnosed between 2014 and 2018, with an average of 551 cases per year.[2] It is the third leading cause of cancer death in men and the fifth in women in Singapore.[3]

A liver cancer surgeon for more than 20 years, Prof Chow leads the Programme in Translational and Clinical Liver Cancer Research at NCCS, which drives comprehensive translational research and clinical studies to better understand and treat HCC. Two national research programmes led by Prof Chow, PLANet (Precision Medicine in Liver Cancer across an Asia-Pacific Network) and ELEGANCE (Early Detection of HCC: miRNA, microbiome and imaging biomarkers in the evolution of chronic liver disease), identified the gut microbiome as a key pathway in liver cancer development, forming the basis for research under his STaR Investigator Award.

The need for early detection and new screening strategies

Only 20% of HCC cases are currently detected early enough when cure is possible.[4] Patients with chronic hepatitis B and C, who make up 4.2% of Singapore’s population, are known to be at very high risk of developing HCC. This group is offered enrolment in life-long screening programmes for HCC so that it can be diagnosed early should it develop. Additionally, patients with Metabolic Dysfunction–Associated Steatotic Liver Disease (MASLD), a condition associated with obesity and metabolic syndrome, are also at increased risk of HCC, though lower than that for chronic viral hepatitis. Patients with MASLD make up 36.5% of all HCC cases in Singapore.[5] Alarmingly, MASLD is on the rise worldwide and in Singapore almost 40% of the population has various degrees of the disease.[6] However, enrolment for this large number of people into lifelong surveillance programs for HCC, which requires twice-a-year ultrasound scans and blood tests, is impractical. It is critical to be able to risk stratify patients with MASLD so that those at higher risk of developing HCC can be enrolled in surveillance programmes.

Determining the gut’s role in liver cancer development

Through the PLANet and ELEGANCE programmes, Prof Chow and his team discovered that dysregulated bile acid is a key risk factor for HCC, particularly in MASLD HCC. This dysregulation is linked to changes in the gut microbiome, which play an important role in digestion, metabolism, and liver health.

Under the STaR Investigator Award, Prof. Chow and his team will:

1. Determine how the role of diet and gut microbiome imbalances contribute to bile acid dysregulation and causes HCC to develop, using data from PLANet and ELEGANCE.

2. Develop a population-level algorithm to predict HCC risk by correlating biomarkers found in PLANet and ELEGANCE against the larger-scale Health for Life in Singapore study (HELIOS, part of SG100K subset) [7] and Singapore Chinese Health Study (SCHS)[8] cohorts.

3. Conduct an interventional study to determine if dietary and lifestyle changes can reverse gut microbiome imbalances and bile acid dysregulation in people with MASLD.

Prof Chow is optimistic about what the results of this study could mean for at-risk populations: "This innovative study aims to identify a strategy for screening individuals without chronic viral hepatitis who are at risk of developing HCC, even if they don’t have traditional risk factors. If we can confirm the mechanisms behind how the gut influences the development of liver cancer, we will be able risk stratify patients so that those with higher risk can be enrolled in screening programs. And we believe that our interventional study will provide the basis for a diet and exercise regime to prevent liver cancer from developing.”

Harnessing immune cells to treat head and neck cancers

The changing profile of head and neck cancers

Head and neck cancers are more common in Asia than in other parts of the world. Traditionally, these cancers were largely seen in men who were heavy smokers and drinkers, but there is a rising incidence in younger patients of both genders, many of whom do not smoke or drink. In Singapore, around 950 new cases are diagnosed each year.[9]  While early-stage head and neck cancers are often treatable, survival rates for advanced cases remain low, with only a 20% survival rate for late-stage diagnoses.

Head and neck surgeon Prof Iyer, who is also Head of Division of Medical Sciences at NCCS, has so far focused his translational research on precision medicine approaches to treat head and neck cancers. With support from the STaR Investigator Award, his team will move their research from the lab to the clinic by harnessing immune cells to treat head and neck cancers with cell therapies.

Using immune cell therapy to target solid tumours

While the use of cell therapy, which harnesses the body’s immune cells to fight disease, has been successful in treating blood cancers, its use in solid tumours remains limited. Tumour-infiltrating lymphocyte (TIL) therapy, a type of cell therapy which involves expanding immune cells from a patient’s tumour and reinfusing them to target and kill cancer cells, has shown promise in treating melanoma. However, to date TIL therapy has not been used to treat cancers that are prevalent in Asia.

Impediments to widespread use of TIL therapy include the centralised manufacturing process, which is limited to pharmaceuticals and existing centres of expertise, the technical complexity needed to produce the therapy and the potential of life-threatening adverse effects in patients. In addition, the current cost of treatment, at around US$500,000 a dose, is prohibitively expensive.

An ambitious plan for SG-produced TIL therapy

To improve his patients’ access to TIL therapy, Prof Iyer and his team have developed a lab-based system to produce the therapy to treat head and neck cancers. This system is ready for conversion to clinical grade protocol to produce a therapy for delivery to patients with advanced head and neck cancers. The team has partnered with collaborators in Netherlands Cancer Institute and Swiss biotech company, Tigen Pharma, with the aim of further refining the production process into an efficient and cost-effective three-week protocol. TILs will be produced on-site at the Advanced Cell Therapy and Research Institute, Singapore (ACTRIS) which is housed in the NCCS building.

Under the STaR Investigator Award, Prof Iyer and his research team aim to establish a TIL-therapy programme for patients with head and neck cancers and advanced solid tumours, by:

1. Conducting a Phase 1b/2 clinical trial to assess the safety and efficacy of TIL therapy for head and neck cancers and other solid tumours.

2. Identifying biomarkers for TIL therapy expansion, to improve efficacy and mitigate adverse events in patients.

3. Refining TIL therapy and developing TIL 2.0, by identifying the most effective immune cell populations, protocol and technique to produce more tumour-targeting TILs based on lab experiments and the Phase 2 trial results.

Prof Iyer is excited about the potential of this homegrown immune cell therapy: “We are standing at the cusp of a new era in cancer treatment. With our expertise, technologies and capabilities at the National Cancer Centre Singapore, we are uniquely positioned to develop and deliver a more cost-effective TIL therapy that could transform the treatment of solid tumours in Singapore and beyond.”

[1] Rumgay, H.; Arnold, M.; Ferlay, J.; Lesi, O.; Cabasag, C. J.; Vignat, J.; Laversanne, M.; McGlynn, K. A.; Soerjomataram, I. Global burden of primary liver cancer in 2020 and predictions to 2040. J Hepatol 2022, 77 (6), 1598-1606. DOI: 10.1016/j.jhep.2022.08.021 

[2] Chew, X. H.; Sultana, R.; Mathew, E. N.; Ng, D. C. E.; Lo, R. H. G.; Toh, H. C.; Tai, D.; Choo, S. P.; Goh, B. K. P.; Yan, S. X.; et al. Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma. Liver Cancer 2021, 10 (3), 224-239. DOI: 10.1159/000514400 

[3] National Registry of Diseases Office. (2024) Singapore Cancer Registry Annual Report 2022.

[4] Bruix, J.; Llovet, J. M. Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology 2002, 35 (3), 519-524. DOI: 10.1053/jhep.2002.32089.

[5] Chew, X. H.; Sultana, R.; Mathew, E. N.; Ng, D. C. E.; Lo, R. H. G.; Toh, H. C.; Tai, D.; Choo, S. P.; Goh, B. K. P.; Yan, S. X.; et al. Real-World Data on Clinical Outcomes of Patients with Liver Cancer: A Prospective Validation of the National Cancer Centre Singapore Consensus Guidelines for the Management of Hepatocellular Carcinoma. Liver Cancer 2021, 10 (3), 224-239. DOI: 10.1159/000514400 

[6] Li, J.; Zou, B.; Yeo, Y. H.; Feng, Y.; Xie, X.; Lee, D. H.; Fujii, H.; Wu, Y.; Kam, L. Y.; Ji, F.; et al. Prevalence, incidence, and outcome of non-alcoholic fatty liver disease in Asia, 1999-2019: a systematic review and meta-analysis. Lancet Gastroenterol Hepatol 2019, 4 (5), 389-398. DOI: 10.1016/S2468-1253(19)30039-1 

[7] The HELIOS (Health for Life in Singapore) Study is a population cohort study of 10,000 Singaporeans aged 30-84 led by the NTU Lee Kong Chian School of Medicine, NHG and Imperial College London that aims to identify environmental, lifestyle and genetic factors that cause disease.

[8] The SCHS (Singapore Chinese Health Study) is one of the largest population-based Asian cohort studies in the world, aiming to build a stable cohort for long-term study of dietary, genetic and environmental determinants of cancer and other diseases. The SCHS recruited 63,257 Chinese men and women in Singapore.

[9] Ferlay J, Ervik M, Lam F, Laversanne M, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2024). Global Cancer Observatory: Cancer Today. Lyon, France: International Agency for Research on Cancer. Available from: https://gco.iarc.who.int/today, accessed [27 Jan 2025]

About the National Cancer Centre Singapore

The National Cancer Centre Singapore (NCCS) is a leading national and regional tertiary cancer centre with specialists who are experts in treating cancer. In addition to offering holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct robust, cutting-edge clinical and translational research. To achieve its vision of being a global leading cancer centre, NCCS offers world-class care and shares its depth of experience and expertise by training local and overseas medical professionals.

To meet growing healthcare needs, the new NCCS building opened in 2023 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, advanced and innovative treatment such as proton therapy is offered at the new Goh Cheng Liang Proton Therapy Centre at NCCS.

About the National Medical Research Council (NMRC) Singapore Translational Research (STaR) Investigator Award

The NMRC STaR Investigator Award was introduced in 2008 and is the pinnacle award given to internationally renowned and outstanding investigators in Translational and Clinical Research (TCR), Health Promotion, Preventive Health, Population Health and Health Services Research (HPHSR), and/or Health Technology.

About the National Medical Research Council (NMRC)

The NMRC was established in 1994 to oversee research funding from the Ministry of Health and support the development and advancement of biomedical research in Singapore, particularly in the public healthcare clusters and medical schools. NMRC engages in research strategy and planning, provides funding to support competitive research grants and core research enablers, and is responsible for the development of clinician scientists through awards and fellowships. The council’s work is supported by the NMRC Office which is part of MOH Holdings Pte Ltd. Through its management of the various funding initiatives, NMRC promotes healthcare research in Singapore, for better health and economic outcomes.