Skip Ribbon Commands
Skip to main content

Research

Translational research for childhood brain and solid tumours is critical in finding new and better ways to treat these diseases, while trying to minimize the harm caused by drugs, radiation or surgery. This requires an integrated approach and a high degree of collaboration between doctors and scientists. In this area, KKH, with its high volume of patients, works in cooperation with research centres within the SingHealth Duke-NUS cluster.

Our clinician-scientists and researchers have a particular focus on paediatric brain tumours, neuroblastoma, paediatric renal tumours, ovarian tumours and sarcomas. Existing local research collaborations involve the National Cancer Centre Singapore, Duke-NUS Graduate Medical School, and the National University of Singapore. Current overseas collaborations include the Hospital for Sick Children, Toronto, and St Jude Children’s Research Hospital, Memphis TN.

Using a translational research pipeline, we adopt a targeted approach to advance scientific findings from basic, to pre-clinical and early clinical development, and on to early phase clinical trials, for various paediatric brain and solid tumours. Given the wide heterogeneity of the diseases of interest, there is tremendous scope for developing personalized medical management informed by specific and precise patient and tumour biology to optimize treatment, thereby improving outcomes.

Current initiatives:

  1. Modeling, Analysis and Translational Therapeutics for Tumours of Childhood (MAT3CH). This platform develops orthotopic patient-derived xenografts (PDX) and in vitro cell line models of paediatric brain and solid tumours, in order to facilitate molecular characterization and evaluation of novel therapies for these diseases. This programme facilitates the molecular characterization of paediatric solid tumours in Asian children for the identification of pathogenic molecular aberrations, comparisons of inter-population variations, and in-vivo evaluation of novel agents for translation into early-phase human trials.

  2. Molecular subtyping of childhood brain tumours. We are examining the molecular profile of childhood brain tumours in our local Asian population, something which is lacking in current international published literature. This will allow for improved risk stratification and treatment allocation according to molecular subtypes. Further developments in improved disease classification and identification of potential genetic aberrations will also facilitate research on discovery of novel drug targets for childhood brain tumours.

  3. Mutational analysis, drug-testing and using circulating tumor cells (CTCs) for disease monitoring of neuroblastoma in Asian patients. In collaboration with the Neurodevelopment and Cancer Laboratory at the Yong Loo Lin School of Medicine, National University of Singapore, we are studying the mutational frequency of known variants as well as discovering whether there are novel genes mutated, and their corresponding functional implications and clinical significance in neuroblastoma within the Asian cohort. We are also interested in evaluating novel compounds that target specific pathways implicated in a subset of neuroblastoma cases, by using our pre-clinical drug-testing platform, for more personalized treatment and management of the disease. To complement this, we are currently also exploring the potential use of CTCs as liquid biopsy for disease monitoring in neuroblastoma and osteosarcoma.

  4. Through the support of the VIVA-KKH Paediatric Brain and Solid Tumour programme, the KKH Department of Pathology and Laboratory Medicine operates a diagnostic NanoString Flex platform for clinical tests and development of novel molecular pathology assays.

    One clinical test currently offered is subtyping of medulloblastoma, which is the most common aggressive brain tumour in children. There are four main subtypes of medulloblastoma which differ in aggressiveness, and hence require different treatment strategies. These four subtypes are reliably differentiated by gene expression profiles, and the NanoString method is a cost-effective and rapid method of doing so. Currently, we are the only centre in Asia performing this test.

    The second clinical test that we have set up is a multiplex paediatric solid tumour gene fusion detection assay also using the NanoString method. Gene fusions are an important category of mutations in paediatric cancer, and identification of specific gene fusions helps in classification of the particular cancer, and in some situations, also provides information on what treatment is likely to be effective for the patient. Previous methods of gene fusion detection checked for genes one at a time, and was laborious, time-consuming and expensive. With the NanoString sarcoma test, we are able to identify any of close to 200 fusion genes in a single test at a very low cost-per-gene and with a very rapid turnaround time. This particular test is a laboratory-developed test set up in collaboration with pathologists at the British Columbia Cancer Agency/Vancouver General Hospital, and we currently receive specimens for testing from throughout Asia.

    Additional NanoString-based tests are being developed, including tests for paediatric brain tumours and cancer immune markers. In addition are next-generation sequencing tests including the Oncomine Childhood Cancer test which sequences close to 200 genes for information on specific mutations that aid in diagnosis and treatment planning. Separately, the next-generation sequencing-based Archer FusionPlex test complements the NanoString sarcoma test in having an additional capability of identifying rare or novel gene fusions in childhood cancer which has proven important for several of our patients with cancers that were hitherto unclassifiable.