- Cancer is the leading cause of death in Singapore, accounting for 28.2% of all deaths from 2017 to 2021
- Singapore Ministry of Health through the National Medical Research Council (NMRC), Office, MOH Holdings, Pte Ltd, has awarded S$50 million in national grants to two multi-institution Singapore teams for precision oncology research aimed at improving outcomes for lymphoma and colorectal cancer
Singapore, 24 May 2024 – Two multi-institution and multidisciplinary Singapore teams of clinician-scientists and researchers have been awarded grants of S$25 million each, by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd, under the NMRC Open Fund-Large Collaborative Grant (OF-LCG) programme. The S$50 million support for cancer research establishes the
SYMPHONY 2.0 and
Colo-SCRIPT research programmes to drive precision oncology research in Singapore aimed at improving the understanding, diagnosis and treatment of lymphoma and colorectal cancer.
Led by the National Cancer Centre Singapore (NCCS), in collaboration with the Agency for Science, Technology and Research (A*STAR), the Cancer Science Institute of Singapore (CSI Singapore) and the Yong Loo Lin School of Medicine (NUS Medicine) at the National University of Singapore (NUS), the National University Cancer Institute, Singapore (NCIS), the National University Hospital (NUH), Lee Kong Chian School of Medicine (LKCMedicine) at Nanyang Technological University, Singapore (NTU Singapore), Singapore General Hospital (SGH) and other institutions, the
SYMPHONY 2.0 (Singapore lYMPHoma translatiONal studY 2.0) research programme will address unmet needs in Asian-centric lymphomas and improve patients’ outcomes by developing cost-effective, accessible, and innovative treatment modalities.
The
Colo-SCRIPT (Colorectal cancer
subtype-specific
research
informs
phenotypes, diagnostics &
treatments) research programme is co-led by NCCS and A*STAR, in collaboration with institutions in the SingHealth-Duke-NUS Academic Medical Centre, the National University Health System (NUHS), NUS, the National Healthcare Group (NHG) and NTU’s LKCMedicine, that will use a subtype-specific approach to improve the understanding of colorectal cancer so that for each subtype, the team can implement prevention and early detection strategies to reduce incidence, and test novel therapies in clinical trials.
Cancer is the leading cause of death in Singapore accounting for 28.2% of all deaths from 2017 to 20211. Cancer incidence has risen over the years making the need to better understand, prevent and treat the disease a pressing need. A key challenge in treating cancer is that cancers are often regarded as homogenous. However, patient data shows that the disease presents differently, with great variance in each individual’s cancer development and response to treatment.
The complexity and heterogeneity of cancer has motivated current research done by both the
SYMPHONY 2.0 and
Colo-SCRIPT teams to develop precision approaches that can be adopted to improve patient outcomes. Recognising the value of these efforts, the OF-LCG provides support to further build on the foundations of existing work done and move these discoveries towards clinical applications.
SYMPHONY 2.0 – Improving outcomes for Asian-centric lymphomas
Lymphomas are the fifth most common cancer in Singapore, with more than 5,000 new cases diagnosed between 2017 and 2021. It is also the most common blood cancer in adolescents and young adults (aged 16-45)2. Alarmingly, the global incidence of lymphoma has surged by 168% since 19753 with this trend indicating that Singapore will face increasing health burden from the disease. Historically, lymphoma subtypes have been more thoroughly studied in Western populations making the advancement of the diagnosis and treatment of Asian-centric lymphomas a challenge.
One example of a lymphoma prevalent in Asian populations is an aggressive form of blood cancer called Natural Killer/T-cell lymphoma (NKTCL). In Asia, 15-20% of all lymphomas are classified as NKTCL, compared to the 5-10% in Western countries. Survival rates for NKTCL are poor and this cancer remains less studied, poorly understood, and has limited treatment options. Even with combination chemotherapy, only 20 to 30% of patients survive beyond five years and as many as 30% of patients do not respond to chemotherapy.4
SYMPHONY 2.0 is a continuation of 10 years of work by this group, under the Translational and Clinical Research (TCR) Flagship Programme and SYMPHONY 1.0, which has laid the groundwork to establish Singapore as a hub of translational and clinical expertise in lymphomas. The group has published over 100 studies on Asian-centric lymphomas in top ranked scientific journals, augmenting understanding of the disease. They have also developed enhanced diagnostic and prognostic tools to guide clinical decision-making and identified biomarkers for response to therapeutics that have been incorporated into clinical assays. In addition, they have trained a genomic model to determine the prognosis of NKTCL patients more precisely.
SYMPHONY 2.0 will build on the expertise and knowledge of the group while leveraging emerging technologies to address unmet needs in Asian-centric lymphomas and improve patient outcomes. The programme will focus on 5 thematic areas, with the goal of delivering 3 key projects – establish a Lymphoma Atlas that centralises patient data for research, determine effective drug combinations for lymphoma patients in clinical trials using AI, and improve accessibility to CAR-T Cell therapy through proof-of-concept studies [See Annex A].
SYMPHONY 2.0 Corresponding Principal Investigator Professor Lim Soon Thye, CEO of NCCS and Senior Consultant in the Division of Medical Oncology at NCCS, and Tanoto Foundation Professor in Medical Oncology said, “Our research programme brings together an extensive network of local collaborators and academic partners to tackle the unmet clinical needs and challenges in lymphoma. The vibrant ecosystem in Singapore, backed by strong infrastructure and talented manpower, enables us to optimise the translation of discoveries from bench to bedside.”
SYMPHONY 2.0 Theme 2 PI Professor Chng Wee Joo, who is Provost’s Chair Professor in the Yong Loo Lin School of Medicine, NUS, and Senior Consultant in the Division of Haematology at NCIS, said, “Translational research is the cornerstone of progress in lymphoma treatment. Support by the NMRC and the OF-LCG programme is crucial in this endeavour, as they provide the necessary funding to support extensive research, clinical trials, and the development of new technologies.”
SYMPHONY 2.0 Theme 5 PI Professor Sebastian Maurer-Stroh, who is Executive Director of A*STAR’s Bioinformatics Institute (BII) said, “By integrating multi-omic and clinical data for rare and common lymphomas, this team is establishing an Asian Lymphoma Atlas which will transform lymphoma care through artificial intelligence.”
Colo-SCRIPT – Harnessing the biology of each subtype of Colorectal Cancer to develop strategies, tailored to each subtype, for prevention, early detection and treatment
In Singapore, colorectal cancer (CRC) is the most common cancer affecting both genders. There were 12,239 new cases of colorectal cancer diagnosed between 2017 and 2021, approximately 7 new cases a day5. CRC originates from pre-cancer lesions called colorectal neoplasia (CRN), or polyps. New evidence from patient samples and research data now show that the early lesions and more advanced tumours may be group into distinct entities or molecular subtypes. Importantly, the biological subtypes of pre-cancer and cancer lesions are connected, with distinct biological programmes activated as the different subtypes of pre-cancers advance to become their respective subtypes of cancer. Despite these diverse characteristics across the different tumours, the detection, workup, clinical characterisation, and management of colorectal cancer is typically performed as if CRC and CRN were a single disease. The team seeks to use the distinct biology of the different subtypes to optimise treatment outcomes.
Colo-SCRIPT is the first national CRC research programme. Leading up to this programme, the clinicians and scientists in the
Colo-SCRIPT team have published research findings in high impact journals, such as Nature Genetics, refining the molecular classification of CRC. Using state-of-the-art techniques such as single cell analyses to profile the patients’ tumours at high resolution, they are beginning to resolve the complex nature of the tumours and reveal how one tumour may be different from the other, and how clinicians may exploit the uniqueness of an individual’s tumour to better tailor precision treatment. As a start, the team is currently evaluating biological features that can be purposed either as blood tests for cancer detection or new drug targets for the different cancer subtypes. More recently, the team has embarked on the use of AI-guided endoscopy for detection of early lesions, particularly of the more aggressive subtypes. The findings can guide the better management and follow-up of individuals harbouring the precancer lesions.
The
Colo-SCRIPT research programme seeks to harness insights on the distinct biology of different molecular subtypes in CRC to guide subtype-specific prevention, diagnosis, and treatment of disease. The programme will enrol 2 national cohorts: SCRIPT 1 and 2 in early and late-stage disease respectively. Through 5 thematic areas (pre-cancer, molecular epidemiology, cellular vulnerabilities, immunotherapy, and diagnostics), the programme will translate research findings to 2 key clinical applications termed “receptables”: (1) improve the prevention and detection of CRC as a long-term strategy for reducing CRC incidence; and (2) bring new drugs into clinical trials for improving treatment outcomes for advanced colorectal cancer patients [See Annex B].
Associate Professor Tam Wai Leong, Deputy Executive Director of A*STAR’s Genome Institute of Singapore (GIS), and Scientific Chair of
Colo-SCRIPT said, “It is increasingly clear that colorectal cancer is composed of distinct molecular subtypes and therefore patients need to be managed and treated differently. The one-size-fits-all approach should no longer be the way forward. By better understanding the underlying mechanisms of the complex disease, we will have an opportunity for early intervention to interrupt disease progression and eventually, develop tailored treatment strategies which are more effective for patients.”
Associate Professor Iain Tan, Senior Consultant in the Division of Medical Oncology, NCCS, Goh Hak Su Professor in Colorectal Surgery and Clinical Chair and Corresponding Principal Investigator of
Colo-SCRIPT said, “We have brought together Singapore’s leading clinicians and scientists in colorectal cancer to embark on a first-of-its-kind subtype-biology focused study that spans the entire clinical trajectory of disease from pre-cancer to advanced cancer. Working together across disciplines and institutions, we are excited to launch this national initiative to tackle our most common cancer. Singapore seeks to pioneer a subtype-specific paradigm for the efficient and effective prevention, diagnosis, and treatment of colorectal cancer.”
The Open Fund-Large Collaborative Grant (OF-LCG) Programme
The OF-LCG grant call aims to bring together the best teams from public institutions to advance human health and wellness, as well as create economic value for Singapore and Singaporeans through the pursuit of excellence in research and its applications.
SYMPHONY 2.0 and
Colo-SCRIPT are supported by the National Research Foundation Singapore (NRF) under the Open Fund-Large Collaborative Grant and administered by the Singapore Ministry of Health through the NMRC Office, MOH Holdings Pte Ltd.
1National Registry of Diseases Office. (2023). Singapore Cancer Registry Annual Report 2021. Retrieved from: https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-ar-2021-web-report.pdf?sfvrsn=591fc02c_0
2National Registry of Diseases Office. (2023). Singapore Cancer Registry Annual Report 2021. Retrieved from: https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-ar-2021-web-report.pdf?sfvrsn=591fc02c_0
3Thandra KC, Barsouk A, Saginala K, et al: Epidemiology of Non-Hodgkin's Lymphoma. Med Sci (Basel) 9, 2021
4Yoon SE, Kim SJ, Kim WS: Overview of the current treatment strategy in extranodal NK/T-cell lymphoma: from diagnosis to recurrence. Annals of Lymphoma 5, 2021
5National Registry of Diseases Office. (2023). Singapore Cancer Registry Annual Report 2021. Retrieved from: https://www.nrdo.gov.sg/docs/librariesprovider3/default-document-library/scr-ar-2021-web-report.pdf?sfvrsn=591fc02c_0
ANNEX A
SYMPHONY 2.0 THEMES AND Pis
Theme 1
| Refining and enhancing lymphoma diagnosis, classification, and risk stratification
Led by Associate Professor Ng Siok Bian, Department of Pathology at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine), and supported by Dr Chen Jinmiao, Bioinformatics Institute (BII) and Institute of Molecular and Cell Biology (IMCB), A*STAR.
|
Theme 2
| Spatial phenotypes of drug resistance in aggressive lymphoma
Led by Assistant Professor Anand Jeyasekharan, Cancer Science Institute of Singapore, NUS, and the National University Cancer Institute, Singapore (NCIS); and supported by Dr Chen Jinmiao, BII and IMCB, A*STAR
|
Theme 3
| Overcoming immune evasion in lymphoma
Led by Associate Professor Ong Choon Kiat, National Cancer Centre Singapore (NCCS), supported by Associate Professor Navin Kumar Verma, Nanyang Technological University, Singapore and Dr Nicholas Grigoropoulos, Singapore General Hospital
|
Theme 4
| Developing novel platforms and assets for therapeutic drug discovery in lymphoma
Led by Professor Chng Wee Joo, NCIS and National University Health System, supported by Associate Professor Olaf Rötzschke, Singapore Immunology Network (SigN)
|
Theme 5
| Transforming lymphoma care through Artificial Intelligence and integration of clinical, molecular and socioenvironmental data
Led by Professor Lim Soon Thye, NCCS, and supported by Asst Prof Valerie Yang, NCCS and IMCB, A*STAR, Dr Woo Xing Yi, BII, A*STAR, and by Dr Chen Jinmiao, BII and IMCB, A*STAR.
|
3 Key Projects:
- Establish the
Lymphoma Atlas for Multidimensional Investigations in Asian populations (LAMINA), a resource for clinician-scientists and scientists that centralises comprehensive patient and preclinical model data, including molecular data, family history, genetics, socioenvironmental factors and psychological data, allowing for a holistic approach to understanding lymphoma. This resource will be driven by Artificial Intelligence (AI) and enable the generation of data and discoveries precisely tailored to characteristics of lymphomas unique in Asian populations.
- Implement
Quadratic Phenotypic Optimized Platform (QPOP), a novel AI-driven digital medicine platform, that can identify 2- or 3-drug combinations, from existing approved drugs, tailored for patients to treat relapsed/refractory (RR) T cell lymphomas as well as refractory aggressive B cell lymphomas as part of a Phase II clinical trial. An example of personalised medicine, it is predicted that that a viable recommendation can be made in approximately 90% of patients and is an example of cost-sensitive personalised healthcare.
- Make
CAR-T cell therapy more accessible and effective for patients with refractory/relapsed aggressive B cell lymphomas. High cost and potential side effects pose significant challenges to widespread adoption of the therapy. The group will conduct proof-of-concept studies to facilitate patient access to CAR-T cell therapies, demonstrating feasibility and effectiveness and pave the way for broader adoption with the ultimate goal of benefitting a larger population of patients.
ANNEX B
Colo-SCRIPT THEMES AND PIs
Theme 1
| Early Carcinogenesis - Decoding early events influencing transitions through pre-invasive to invasive cancer
Led by Professor Ashok Venkitaraman, Cancer Science Institute of Singapore, NUS and Institute of Molecular and Cell Biology (IMCB), A*STAR, and Dr Shyam Prabhakar, Genome Institute of Singapore (GIS), A*STAR
|
Theme 2
| Molecular Epidemiology - Establishing the role of environmental, metabolic and microbial risk factors enabling disease progression
Led by Professor Vinay Tergaonkar, IMCB, A*STAR and Associate Professor Sunny Wong, Nanyang Technological University, Singapore
|
Theme 3
| Cellular Vulnerabilities - Harnessing functional genomics to discover subtype-specific (epi)-genetic & metabolic dependencies to expose therapeutic vulnerabilities
Led by Associate Professor Tam Wai Leong, GIS, A*STAR and Professor Patrick Tan, Duke-NUS Medical School
|
Theme 4
| Tumour Immunology - Deciphering the tumour immune microenvironment (TIME) for improving immunotherapies
Led by Associate Professor Iain Tan, National Cancer Centre Singapore (NCCS) and Professor Li Qi-Jing, IMCB and Singapore Immunology Network (SIgN), A*STAR
|
Theme 5
| Detection & Characterisation - Developing diagnostic tools for subtype-specific clinical detection & characterisation
Led by Professor Joseph Sung, Nanyang Technological University, Singapore and Professor Tony Lim, Singapore General Hospital
|
2 Key Receptacles:
-
Prevent and detect CRC early to improve population health and reduce economic burden associated with disease progression. Through the recruitment of 20,000 individuals undergoing in the SCRIPT-1 clinical cohort, the team will develop new subtype-specific diagnostic methods and investigate the influence of genetic, environmental, metabolic and microbial risk factors on CRN and CRC subtypes.
Key Projects: (1)
Pre-cancer atlas: detailed characterization and experimental study of the early molecular events that mediate the transition from normal colon to pre-cancer to early cancer of each subtype. Integrated with environmental influences, findings may inform cancer prevention. (2)
Early detection methods: The team will develop new non-invasive blood and stool tests and new AI-enabled endoscopy methods to complement or improve current screening methods for improved detection of different CRN/CRC subtypes.
-
Develop therapies for patients with advanced colorectal cancers by identifying subtype-specific targets and implement novel therapeutics for disease intervention. 1,000 patients will be recruited for the SCRIPT-2 clinical cohort to build a biospecimen repository and develop patient-specific tumour models for the deep profiling of tumour subtypes. The findings are expected to empower large-scale therapeutic trials aimed at precision treatment of CRC.
Key Projects: (1)
Cellular vulnerabilities: detailed study of the epigenetic and metabolic dependencies of the different CRC subtypes will provide candidate targets which will be evaluated in patient-specific tumour models, leading to development of subtype-specific therapeutics; (2)
Immunotherapy: Examining mechanisms by which different subtypes of cancers evade host immune control, the team will identify and develop biopharmaceuticals and cellular therapies, particularly CAR-T cell therapies that are specifically effective against respective subtypes.
-END-
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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.
In 2024, NCCS celebrates its silver anniversary, celebrating 25 years of advancing cancer care from breakthroughs to healing.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis. For ongoing news, visit www.a-star.edu.sg.
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About Nanyang Technological University, Singapore
A research-intensive public university, Nanyang Technological University, Singapore (NTU Singapore) has 33,000 undergraduate and postgraduate students in the Engineering, Business, Science, Medicine, Humanities, Arts, & Social Sciences, and Graduate colleges.
NTU is also home to world-renowned autonomous institutes – the National Institute of Education, S Rajaratnam School of International Studies and Singapore Centre for Environmental Life Sciences Engineering – and various leading research centres such as the Earth Observatory of Singapore, Nanyang Environment & Water Research Institute and Energy Research Institute @ NTU (ERI@N).
Under the NTU Smart Campus vision, the University harnesses the power of digital technology and tech-enabled solutions to support better learning and living experiences, the discovery of new knowledge, and the sustainability of resources.
Ranked amongst the world’s top universities, the University’s main campus is also frequently listed among the world’s most beautiful. Known for its sustainability, NTU has achieved 100% Green Mark Platinum certification for all its eligible building projects. Apart from its main campus, NTU also has a medical campus in Novena, Singapore’s healthcare district.
For more information, visit www.ntu.edu.sg
About the National University Health System (NUHS)
The National University Health System (NUHS) aims to transform how illness is prevented and managed by discovering causes of disease, development of more effective treatments through collaborative multidisciplinary research and clinical trials, and creation of better technologies and care delivery systems in partnership with others who share the same values and vision.
Institutions in the NUHS Group include the National University Hospital, Ng Teng Fong General Hospital, Jurong Community Hospital and Alexandra Hospital; three National Specialty Centres – National University Cancer Institute, Singapore (NCIS), National University Heart Centre, Singapore (NUHCS) and National University Centre for Oral Health, Singapore (NUCOHS); the National University Polyclinics (NUP); Jurong Medical Centre; and three NUS health sciences schools – NUS Yong Loo Lin School of Medicine (including the Alice Lee Centre for Nursing Studies), NUS Faculty of Dentistry and NUS Saw Swee Hock School of Public Health.
With member institutions under a common governance structure, NUHS creates synergies for the advancement of health by integrating patient care, health science education and biomedical research.
As a Regional Health System, NUHS works closely with health and social care partners across Singapore to develop and implement programmes that contribute to a healthy and engaged population in the Western part of Singapore.
For more information, please visit www.nuhs.edu.sg.
About National University of Singapore (NUS)
The National University of Singapore (NUS) is Singapore’s flagship university, which offers a global approach to education, research and entrepreneurship, with a focus on Asian perspectives and expertise. We have 16 colleges, faculties and schools across three campuses in Singapore, with more than 40,000 students from 100 countries enriching our vibrant and diverse campus community. We have also established more than 20 NUS Overseas Colleges entrepreneurial hubs around the world.
Our multidisciplinary and real-world approach to education, research and entrepreneurship enables us to work closely with industry, governments and academia to address crucial and complex issues relevant to Asia and the world. Researchers in our faculties, research centres of excellence, corporate labs and more than 30 university-level research institutes focus on themes that include energy; environmental and urban sustainability; treatment and prevention of diseases; active ageing; advanced materials; risk management and resilience of financial systems; Asian studies; and Smart Nation capabilities such as artificial intelligence, data science, operations research and cybersecurity.
For more information on NUS, please visit nus.edu.sg.
About Singapore General Hospital (SGH)
Singapore General Hospital, a member of Singapore Health Services, is the public sector's flagship hospital. Established in 1821, SGH is Singapore's largest tertiary hospital with 1,700 beds and national referral centre offering a comprehensive range of more than 40 clinical specialties on its campus. Every year, about 1 million Singaporeans benefit from medical care delivered by its 800 specialists. As an academic healthcare institution and the bedrock of medical education. SGH plays a key role in nurturing doctors, nurses and allied health professionals, and is committed to innovative translational and clinical research in her continual strive to provide the best care and outcomes to her patients.
For more information, please visit www.sgh.com.sg
About SingHealth Duke-NUS Academic Medical Centre
The SingHealth Duke-NUS Academic Medical Centre (AMC) draws on the collective strengths of SingHealth and Duke-NUS Medical School to provide our patients and community with the best outcomes and experience.
By leveraging the synergies in clinical care, research and education created through our Academic Clinical Programmes, Disease Centres and Joint Institutes, the SingHealth Duke-NUS AMC fosters the exchange of scientific knowledge and clinical perspectives to accelerate innovation and new discoveries, advance the practice of medicine as well as nurture the next generation of healthcare professionals.
SingHealth delivers comprehensive, multi-disciplinary and integrated care across a network of acute hospitals, national specialty centres, polyclinics and community hospitals. Offering over 40 clinical specialties, SingHealth is Singapore’s largest public healthcare cluster.
Duke-NUS, Singapore’s flagship graduate-entry medical school, nurtures ‘Clinician Plus’ graduates to become leaders in the global healthcare and biomedical ecosystem, while scientists from its five Signature Research Programmes and 10 Centres transform medicine and improve lives in Asia and beyond.
For more information, please visit: www.singhealthdukenus.com.sg
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About the National Medical Research Council (NMRC)
The NMRC was established in 1994 to oversee research funding from the Singapore Ministry of Health (MOH) 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.