Skip Ribbon Commands
Skip to main content

Signature Research Programs

Singapore Lymphoma Study (SLS)

​In Singapore, lymphoid neoplasms are the 5th and 6th most common cancer in males and females, respectively. Including Singapore, there is a global trend of rising incidence which led to the beginning of the Singapore Lymphoma Study in January 2005.

Currently, epidemiology and clinical data on lymphoid neoplasms is derived mainly from Western series. An increasing body of information from our center and collaborations with other healthcare institutions suggest that geographic localities as well as ethnicity are important factors and extrapolation of experience and data from the West to the Asian setting may have limitations. More importantly, the detailed clinical and molecular data obtained from this study will form the basis of all future research and healthcare planning.

The main purpose of the Singapore Lymphoma Study (SLS) is to exhaustively evaluate the molecular characteristics of lymphoma, particular subtypes that occur at higher frequencies in Asians and subsequently to develop new biomarkers, diagnostic assays, treatment targets and novel treatment strategies, particularly against lymphoma subtypes unique to Asians.

Headed by Prof Lim Soon Thye (Deputy Group Chief Executive Officer (Research & Education), SingHealth, Deputy Chief Executive Officer (Clinical) of National Cancer Centre Singapore (NCCS), Professor at the DukeNUS Graduate Medical School, Singapore and Lead Principal Investigator of the Translational and Clinical Research (TCR) and Large Collaborative Grant Programme for Lymphoma), the SLS aims to examine the clinical and pathological profile of lymphoid malignancies (non-Hodgkin lymphoma and Hodgkin lymphoma) in Singapore with respect to mode of presentation, clinical features, histologic and immunophenotypic distribution. Comprising of clinicians, pathologists, epidemiologists and scientists from all institutes across Singapore, namely: National Cancer Centre Singapore (NCCS), Singapore General Hospital (SGH), Singapore National Eyes Centre (SNEC), Duke-NUS Medical school, Genome Institute of Singapore (GIS), Singapore Immunology Network (SIgN), Institute of Molecular and Cell Biology (IMCB), National University Hospital System (NUHS), Cancer Science Institute (CSI), Nanyang Technological University (NTU) and Tan Tock Seng Hospital (TTSH), the group hopes to elucidate the genetic drivers of disease initiation and progression, and to evaluate the risk profile of lymphoid malignancies associated with lifestyle factors (e.g. fruit/vegetables, meat intake, alcohol consumption and use of hair dyes), exposure to specific infectious agents and occupational exposure to pesticides and benzene.

The SLS forms a major component of the awarded S$10 Million Large Collaborative Grant (LCG) project titled “The Singapore lYMPHoma translatiONal studY (SYMPHONY)”, a continuation of the National Lymphoma Translational and Clinical Research (TCR) Programme (2014 - 2019), which is supported by the National Medical Research Council (NMRC). The SYMPHONY programme has provided major breakthroughs including identifications of novel mutations in key signaling pathways and identification of novel immune escape mechanisms. It brings together clinicians and scientists across Singapore to work in collaboration with local biotech enterprises and international pharmaceutical companies, as well as global academic centres to address the worldwide unmet clinical needs in the management of these malignancies (Sun Yat-Sen University Cancer Centre, Guangdong Provincial People’s Hospital, Samsung Medical Centre, MD Anderson, Queen Mary Hospital, Massachusetts Institute of Technology, University of Nebraska and Medical Center). The team will continue to channel resources into bringing the programme to greater heights while maintaining our avenue as a centre for excellence in therapeutic targeting of lymphoma to ensure that research into mechanisms of lymphoma can be effectively translated into the healthcare settings in a cost effective manner.

Selected Publications:

  1. Koo GC, Tan SY, Tang T, et al: Janus Kinase 3–Activating Mutations Identified in Natural Killer/T-cell Lymphoma. Cancer Discovery 2:591-597, 2012.
  2. Song TL, Nairismagi ML, Laurensia Y, et al: Oncogenic activation of the STAT3 pathway drives PD-L1 expression in natural killer/T-cell lymphoma. Blood 132:1146-1158, 2018.
  3. Nairismagi M, Gerritsen ME, Li ZM, et al: Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma. Leukemia 32:1147-1156, 2018.
  4. Huang D, Song TL, Nairismägi ML, et al: Evaluation of the PIK3 pathway in peripheral T-cell lymphoma and NK/T-cell lymphoma. Br J Haematol. 189(4):731-744, 2020.
  5. Peng R-J, Han B-W, Cai Q-Q, et al: Genomic and transcriptomic landscapes of Epstein-Barr virus in extranodal natural killer T-cell lymphoma. Leukemia 33:1451-1462, 2019.
  6. Kwong YL, Chan TSY, Tan D, et al: PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 129(17):2437-2442, 2017.
  7. Kim SJ, Lim JQ, Laurensia Y, et al: Avelumab for the treatment of relapsed or refractory extranodal NK/T-cell lymphoma: an open-label phase 2 study. Blood. 2020 Aug 7.
  8. Lim JQ, Huang D, Tang T, et al: Whole-genome sequencing identifies responders to Pembrolizumab in relapse/refractory natural-killer/T cell lymphoma.. Leukemia. 2020 Aug 5.
  9. Ngeow KC, Choudhury Y, Tan D, et al: Ultrasensitive multiplex detection of structural rearrangements in ALK, RET, ROS1 and PD-L1 using a comprehensive next-generation sequencing assay. ASCO 2020 poster abstract 3572.
  10. Li Z, Xia Y, Feng LN, et al: Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study. Lancet Oncol 17:1240-7, 2016.
  11. Lin GW, Xu C, Chen K, et al: Genetic risk of extranodal natural killer T-cell lymphoma: a genome-wide association study in multiple populations. Lancet Oncology 21(2):306-316, 2020.
  12. Chan JY, Ng AYJ, Cheng CL, et al: Whole exome sequencing identifies recessive germline mutations in FAM160A1 in familial NK/T cell lymphoma. Blood cancer journal 8:111-111, 2018.
  13. Ong SY, Lim JQ, Grigoropoulos N, et al: No association between ECSIT germline mutations and hemophagocytic lymphohistiocytosis in natural killer/T-cell lymphoma. Haematologica. 2021 Oct 13.
  14. Nairismagi ML, Tan J, Lim JQ, et al: JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia 30:1311-9, 2016.
  15. Huang D, Lim JQ, Cheah DMZ, et al: Whole-genome sequencing reveals potent therapeutic strategy for monomorphic epitheliotropic intestinal T-cell lymphoma. Blood Adv. 4(19):4769-4774, 2020.
  16. de Mel S, Rashid MBM, Zhang XY, et al: Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma. Blood Cancer J. 10(1):9. 2020.
  17. Tan KM, Chia B, Lim JQ, et al: A clinicohaematological prognostic model for nasal-type natural killer/T-cell lymphoma: A multicenter study. Scientific Reports 9:14961, 2019.
  18. Tian XP, Ma SY, Young KH, et al. A composite single-nucleotide polymorphism prediction signature for extranodal natural killer/T-cell lymphoma [published online ahead of print, 2021 Mar 16]. Blood. 2021; blood.2020010637.
  19. Ng SB, Chung TH, Kato S, et al: Epstein-Barr virus-associated primary nodal T/NK-cell lymphoma shows a distinct molecular signature and copy number changes. Haematologica 103:278-287, 2018.
  20. Heavican TB, Bouska A, Yu J, et al: Genetic drivers of oncogenic pathways in molecular subgroups of peripheral T-cell lymphoma. Blood 133:1664-1676, 2019.
  21. Amador C, Greiner TC, Heavican TB, et al: Reproducing the Molecular Subclassification of Peripheral T-cell Lymphoma-NOS by Immunohistochemistry. Blood, 2019.
  22. Oon ML, Lim JQ, Lee B, et al: T-Cell Lymphoma Clonality by Copy Number Variation Analysis of T-Cell Receptor Genes. Cancers (Basel) 13(2):340, 2021
  23. Lone W, Bouska A, Sharma S, et al: Genome-Wide miRNA Expression Profiling of Molecular Subgroups of Peripheral T-cell Lymphoma. Clin Cancer Res, 2021
  24. Mustafa N, Nee AHF, Chooi JY, et al: Determinants of response to daratumumab in Epstein-Barr virus-positive natural killer and T-cell lymphoma. Journal for immunotherapy of cancer 9:e002123, 2021
  25. Kizhakeyil A, Zaini NBM, Poh ZS, et al: DDX3X loss is an adverse prognostic marker in diffuse large B-cell lymphoma and is associated with chemoresistance in aggressive non-Hodgkin lymphoma subtypes. Mol Cancer 20:134, 2021
  26. Gong C, Krupka JA, Gao J, et al: Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Mol Cell 81:4059-4075.e11, 2021
  27. Sun Y, Gao Y, Chen J, et al: CREBBP cooperates with the cell cycle machinery to attenuate chidamide sensitivity in relapsed/refractory diffuse large B-cell lymphoma. Cancer Lett 521:268-280, 2021
  28. Wai CMM, Chen S, Phyu T, et al: Immune pathway upregulation and lower genomic instability distinguish EBV-positive nodal T/NK-cell lymphoma from ENKTL and PTCL-NOS. Haematologica, 2022
  29. Lim JQ, Lim ST, Ong CK: Misaligned sequencing reads from the GNAQ-pseudogene locus may yield GNAQ artefact variants. Nature Communications 13:458, 2022
  30. Zhou J, et al. Super-enhancer-driven TOX2 mediates oncogenesis in Natural Killer/T Cell Lymphoma. Mol Cancer. 2023 Apr 10;22(1):69.
  31. Chen J, et al. Aberrant JAK-STAT signaling-mediated chromatin remodeling impairs the sensitivity of NK/T-cell lymphoma to chidamide. Clin Epigenetics. 2023 Feb 6;15(1):19.
  32. Lim JQ, et al. A genomic-augmented multivariate prognostic model for the survival of Natural-killer/T-cell lymphoma patients from an international cohort. Am J Hematol. 2022 Sep;97(9):1159-1169
  33. Wang Y, Zhou W, Chen J, et al: Preclinical characterization of WB737, a potent and selective STAT3 inhibitor, in natural killer/T-cell lymphoma. MedComm (2020) 4:e284, 2023
  34. Poh J, Ngeow KC, Pek M, et al: Analytical and clinical validation of an amplicon-based next generation sequencing assay for ultrasensitive detection of circulating tumor DNA. PLoS One 17:e0267389, 2022
  35. Goh J, De Mel S, Hoppe MM, et al: An ex vivo platform to guide drug combination treatment in relapsed/refractory lymphoma. Sci Transl Med 14:eabn7824, 2022
  36. Herek TA, Bouska A, Lone W, et al: DNMT3A mutations define a unique biological and prognostic subgroup associated with cytotoxic T cells in PTCL-NOS. Blood 140:1278-1290, 2022
  37. Amador C, Bouska A, Wright G, et al: Gene Expression Signatures for the Accurate Diagnosis of Peripheral T-Cell Lymphoma Entities in the Routine Clinical Practice. J Clin Oncol 40:4261-4275, 2022
Lung Cancer Consortium Singapore (LCCS)

The Lung Cancer Consortium Singapore (LCCS) was first established with the aim of bringing together the clinical and research community in order to advance the diagnosis and management of thoracic cancers. The need to set up the Consortium was driven by differences in lung cancer profiles and survival outcomes observed between the East and West. The research study, now known as National Lung Cancer Research (NLCR), was piloted in 2001 by Dr Tan Eng Huat to study the molecular profile of lung cancer in our local context, in collaboration with SingHealth institutions including SGH and CGH. LCCS was formally set up and expanded to other public hospitals including NUH and TTSH in 2007, with the aim of building infrastructure to promote and support nationwide collaboration for lung cancer research. The collaboration was further expanded to researchers in the Agency for Science, Technology and Research (A*STAR) in 2013, with the funding support from MOH National Medical Research Council (NMRC). Under the NLCR, clinical and lifestyle questionnaire data, as well as biological material, are collected in order to study epidemiological characteristics and treatment outcomes of various lung cancer subtypes in Singapore, as well as to conduct translational work. Since its inception, LCCS has facilitated collaborations that have generated several high impact factor publications at prestigious journals, including Nature Medicine, Nature Communications, Nature Genetics, Immunity, and Journal of Clinical Oncology, amongst others.

Many lung cancer patients have contributed to our research efforts. To date, over 6000 patients have been enrolled to the study. Recruitment is ongoing.

Other than research work, LCCS also conducts other lung cancer-related activities, with an emphasis on promoting education to both physicians and the public. A few events have been organized by LCCS in the past few years, which include:

  • Multi-disciplinary lung cancer conference (MLCC) to educate and share knowledge for local and regional professionals
  • Inter-Disciplinary Workshop to Enhance Assessment and Management of Lung Cancer (IDEAL), a lung cancer preceptorship programme for trainees across different specialties involved in the management of thoracic malignancies
  • LCCS forum to bring together clinicians and researchers across Singapore, both from the public and private sectors
  • Public talks

A relatively new initiative, the Lung Cancer Education and Advocacy for Patients (LEAP) program has been set up in Q3 2019 with the inaugural patient support group meeting held in the Lung Cancer Awareness Month (LCAM) Nov 2019. LEAP aims to support lung cancer patients in Singapore through providing educational resources on the disease, and creating awareness through our patient advocacy group. A few webinars have been organized during COVID-19 pandemic period with good support from various parties. A patient navigator program is also in place to guide patients on their disease journey.

More information about LCCS and LEAP can be found here.

Clinical Trial Program

NCCS is at the forefront of cancer clinical research in Singapore that is aimed at developing novel and up-to-date treatments to improve the lives of patients with different cancer types, including breast, lung, nasopharyngeal, stomach, colorectal and liver cancers. We have over a decade of experience in conducting clinical trials and have completed a broad spectrum of more than a hundred clinical trials to date. Our portfolio encompasses phases I to III trials, with most studies evaluating the effectiveness of novel molecular targeted agents.

In the Division of Medical Oncology, our investigators have been heavily involved in conducting and leading both Pharma-sponsored trials and Investigator-initiated trials across a wide spectrum of cancer types. They are working closely with Clinical Trials & Epidemiological Sciences department (CTE), in the conduct of these trials.

Cancer Genetics Service (CGS)

​The Cancer Genetics Service (CGS) is the clinical arm of the broader Hereditary Cancer and Rare Disease Translational Research Programme. It is currently led by Dr Joanne Ngeow, a senior consultant in the Division of Medical Oncology, National Cancer Centre Singapore.

The mission of Cancer Genetics Service (CGS) is to serve as an expert base in the principles and practice of genetic and genomic medicine as a single platform for research, academic clinical practice, and education for NCCS, SingHealth and Singapore. This is to ensure that personalised healthcare is based on rigorously researched and validated genetic information that can be incorporated into routine oncological care. The CGS serves as a self-and physician-referral-based clinical centre that provides expert genetic risk assessment for a broad array of diseases, education, genetic counselling, targeted gene testing, medical management recommendations and appropriate multi-specialty referrals. It is unique because the comprehensive clinical practice of medical genetics and genomic medicine is housed under one roof in proximity to the research on which the evidence-based practice of personalised genetic healthcare is performed.

The CGS is staffed by medical oncologists with advanced specialisation in cancer genetics and a team of genetic counsellors. They are internationally known for their specialisation in breast, endocrine-related, gastrointestinal and urological cancers, highlighted by active and on-going contributions to cancer genetics.

The CGS carries the full suite of genetic medicine services, ranging from genetics of adult-onset disorders, such as cancer predisposition syndromes, to rare metabolic disorders. Patient visits to the CGS are set to increase with greater awareness of the role genomics plays in modern day cancer care. Common conditions seen at the CGS include Hereditary Breast and Ovarian Cancer Syndrome, Lynch syndrome, Hereditary Paraganlioma and Pheochromocytoma syndrome, Li Fraumeni syndrome and other cancer predisposition syndromes.

Experimental Cancer Therapeutics Unit (ECRU)

​The Experimental Cancer Therapeutics Unit (ECRU) was set up in 2009. It is part of the Division of Medical Oncology and headed by Dr Daniel Tan, a senior consultant in the Division of Medical Oncology, National Cancer Centre Singapore.

The primary mission of ECRU is to bring novel therapeutic options to the clinic while concomitantly advancing the understanding of cancer biology through the design of science-driven trials. Its focus is on providing a single point of engagement for the conduct of Phase 0/1/2 trials. Through this unique translational interface, ECRU works closely with scientists in NCCS, Duke-NUS, GIS and others, in order to increase the value of Phase I trials beyond simple dose-finding studies. The unit coordinates the aspects of modern drug development from target discovery and validation, xenograft drug screening, clinical pharmacology and biomarker correlative clinical trials. This includes the ability to do sequential tumour biopsies for biomarker development in certain trials. ECRU’s core interests cover all solid tumours and lymphomas.

From conceptualization to the execution of biomarker intense Phase I trials, ECRU has successfully amassed more than SGD 5 million in competitive grants as well as completed more than 50 clinical trials. In 2019, 73 patients out of 212 new referrals were enrolled into Phase I trials including first-in-human studies.

Adolescents and Young Adults Oncology (AYAO) Singapore

The Adolescents and Young Adults Oncology (AYAO) Programme was set up in 2017 and is headed by Dr. Eileen Poon, a consultant in the Division of Medical Oncology, National Cancer Centre Singapore. The AYAO team is a group of passionate and enthusiastic multidisciplinary team who has come together with one main aim – to better the care and lives of AYAO. What started off as a group of individuals doing isolated individual activity sessions has now morphed into a team working to establish a proper clinical service for this group of patients.

We believe that a proper dedicated AYAO service will allow us to provide a complementary individualized service to each of our AYAs. The AYAO Programme aims to provide holistic counselling to address psychosocial, diet and nutrition, exercise, cancer education, sexuality and intimacy, fertility preservation, tissue banking, clinical trials-related matters, finances, or reintegration issues. These issues will allow better compliance and adherence to treatment and hence a better outcome in the long run.

Although cancer is rare in this age group, it still affects 5-10% of those 16-45 years old. It is also the leading cause of death in this age group. NCCS has seen >6000 AYA patients between 2018 – 2021. This number is likely to continue to grow as we expect >80% of our AYAs to survive long-term. If we were to include the population of patients who are childhood cancer survivors transiting into adult care, this number of survivors is going to be humongous. More needs to be done to ensure that survivorship care needs are taken care of well.

We need to recognise and address the unique circumstances related to lifestyle, work, school, family life, and emotional development that young adults face when living with cancers.

The AYAO Programme’s mission is to:
Empower an AYAO to live well THROUGH cancer, and not just LIVE through a cancer diagnosis.