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24 May 2024

• Cancer is the leading cause of death in Singapore, accounting for 28.2% of all deaths from 2017 to 2021
• òòò½ÍøMinistry 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 òòò½Íøteams for precision oncology research aimed at improving outcomes for lymphoma and colorectal cancer

Singapore, 24 May 2024 – Two multi-institution and multidisciplinary òòò½Íøteams of clinician-scientists and researchers have been awarded grants of S$25 million each, by the òòò½ÍøMinistry 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 òòò½Íøaimed at improving the understanding, diagnosis and treatment of lymphoma and colorectal cancer. 

Led by the National Cancer Centre òòò½Íø(NCCS), in collaboration with the òòò½Íø, Technology and Research (A*STAR), the Cancer Science Institute of òòò½Íø(CSI Singapore) and the Yong Loo Lin School of Medicine (NUS Medicine) at the National University of òòò½Íø(NUS), the National University Cancer Institute, òòò½Íø(NCIS), the National University Hospital (NUH), Lee Kong Chian School of Medicine (LKCMedicine) at Nanyang Technological University, òòò½Íø(NTU Singapore), òòò½ÍøGeneral 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 òòò½Íøaccounting for 28.2% of all deaths from 2017 to 2021.¹ 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 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 òòò½Íøwill 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 òòò½Íøas 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 day.⁵ 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 òòò½Íø(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. òòò½Íøseeks 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 òòò½Íøand Singaporeans through the pursuit of excellence in research and its applications.

SYMPHONY 2.0 and Colo-SCRIPT are supported by the National Research Foundation òòò½Íø(NRF) under the Open Fund-Large Collaborative Grant and administered by the òòò½ÍøMinistry of Health through the NMRC Office, MOH Holdings Pte Ltd

ANNEX A

SYMPHONY 2.0 THEMES AND Pis

3 Key Projects:

1. 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.
   
2. 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.
   
   
3. 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

2 Key Receptacles:

1. 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.
   
   
2. 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.

¹ National Registry of Diseases Office. (2023). òòò½ÍøCancer Registry Annual Report 2021. Retrieved from:
² National Registry of Diseases Office. (2023). òòò½ÍøCancer Registry Annual Report 2021. Retrieved from:
³ Thandra KC, Barsouk A, Saginala K, et al: Epidemiology of Non-Hodgkin's Lymphoma. Med Sci (Basel) 9, 2021
⁴ Yoon 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
⁵ National Registry of Diseases Office. (2023). òòò½ÍøCancer Registry Annual Report 2021. Retrieved from:

For media queries and clarifications, please contact:

Eliza Lim (Ms)
Senior Manager, Office of Corporate Communication and Office of Research Planning
A*STAR’s Genome Institute of òòò½Íø(GIS)
Email: Eliza_Lim@gis.a-star.edu.sg

òòò½Íø’s Genome Institute of òòò½Íø(GIS)

The Genome Institute of òòò½Íø(GIS) is an institute of the òòò½Íø, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to achieve extraordinary improvements in human health and public prosperity. Established in 2000 as a centre for genomic discovery, the GIS pursues the integration of technology, genetics, and biology towards academic, economic and societal impact, with a mission to "read, reveal and (ω)rite DNA for a better òòò½Íøand world".

Key research areas at the GIS include Precision Medicine & Population Genomics, Genome Informatics, Spatial & Single Cell Systems, Epigenetic & Epitranscriptomic Regulation, Genome Architecture & Design, and Sequencing Platforms. The genomics infrastructure at the GIS is also utilised to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.

For more information about GIS, please visit www.a-star.edu.sg/gis.

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About the òòò½Íø, Technology and Research (A*STAR)

The òòò½Íø, 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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