$6mil Centre Grant over 3 years (2010-2013), funded by National Medical Research Council
National University Hospital
5 Lower Kent Ridge Road
Main Building, Level 2
Aims and Research Theme
The overall research focus comprises of 5 programs that are tumour-centric but which will focus on 3 major research themes:
- Development of prognostic and predictive assays to individualize therapy
- Development of novel therapies
- Understanding of genetic risk factors in cancer.
These scans show a patient with advanced lung cancer, who had failed standard therapy, responding well to a novel drug undergoing development at the National University Cancer Institute, Singapore (NCIS) and the pharmaceutical industry. Many Singaporeans benefit from research done at NCIS, long before some drugs are commercially available.
In addition, inter-ethnic studies will be integrated in the overall programme with emphasis on elucidating differences in drug disposition and disease biology. Each tumour-centric program is led by established clinician researchers who have access to the appropriate clinical materials, supported by bench and discovery science researchers, and anchored by clinician-scientists who will serve as the bridge between clinician researchers and bench scientists.
The current research programme will encompass two common cancers (breast and lung), two endemic cancers (nasopharyngeal and stomach) and haematological malignancies. Breast and lung cancers are important common cancers with significant disease burden and mortality, and improvements in the understanding and management of these cancers will have significant clinical and health economic impact not only within Singapore but also globally.
Nasopharyngeal and stomach cancers are endemic cancers in Asia, and offer unique opportunities for local researchers to distinguish themselves internationally in the field of cancer research. And while haematological malignancies are less common than solid tumours, they are ideal models to elucidate biological pathways in cancer and for in-depth genetic interrogation as they are clonal and homogeneous, as opposed to solid tumours.
One important distinguishing characteristic of the tumour research teams featured in this programme is that each team comprises of clinicians, clinician-scientists and researchers who have demonstrated fruitful and successful collaborations in translational research based on local patient materials in the past few years. Several of the research teams have distinguished themselves in experimental therapeutics and predictive oncology (NPC, breast), and have demonstrated their ability to secure external competitive research funding.
Sanada M, Suzuki T, Shih LY, Otsu M, Kato M, Yamazaki S, Tamura A, Honda H, Sakata-Yanagimoto M, Kumano K, Oda H, Yamagata T, Takita J, Gotoh N, Nakazaki K, Kawamata N, Onodera M, Nobuyoshi M, Hayashi Y, Harada H, Kurokawa M, Chiba S, Mori H, Ozawa K, Omine M, Hirai H, Nakauchi H, Koeffler HP, Ogawa S. Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms. Nature. 2009 Aug 13;460(7257):904-8.
Hsieh WS, Soo R, Peh BK, Loh T, Dong D, Soh D, Wong LS, Green S, Chiao J, Cui CY, Lai YF, Lee SC, Mow B, Soong R, Salto-Tellez M, Goh BC. Pharmacodynamic effects of seliciclib, an orally administered cell cycle modulator, in undifferentiated nasopharyngeal cancer. Clin Cancer Res. 2009 Feb 15;15(4):1435-42.
K S Loh, B C Goh, Jay Lu, W S Hsieh, L K S Tan. Familial nasopharyngeal carcinoma in a cohort of 200 patients. Arch Otolaryngol Head Neck Surg. 2006 Jan; 132(1):82-5.
Yeoh EJ, Ross ME, Shurtleff SA, Williams WK, Patel D, Mahfouz R, Behm FG, Raimondi SC, Relling MV, Patel A, Cheng C, Campana D, Wilkins D, Zhou X, Li J, Liu H, Pui CH, Evans WE, Naeve C, Wong L, Downing JR. Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. Cancer Cell. 2002 Feb; 1(1):63-74.
Chng WJ, Braggio E, Mulligan G, Bryant B, Remstein E, Valdez R, Dogan A, Fonseca R. The centrosome index is a powerful prognostic marker in myeloma and identifies a cohort of patients that might benefit from aurora kinase inhibition. Blood. 2008 Feb 1; 111(3):1603-9.
Chia KS, Reilly M, Tan CS, Lee J, Pawitan Y, Adami HO, et al. Profound changes in breast cancer incidence may reflect changes into a Westernized lifestyle: a comparative population-based study in Singapore and Sweden. Int J Cancer 2005; 113(2):302-6.
Hartman M, Loy EY, Ku CS, Chia KS, Molecular epidemiology and its current clinical utility in cancer management, Lancet Onc 2010. (Accepted)
Lim YK, Iau PT, Ali AB, Lee SC, Wong JE, Putti TC, Sng JH. Identification of novel BRCA large genomic rearrangements in Singapore Asian breast and ovarian patients with cancer. Clin Genet. 2007; 71(4): 331-42.
Ooi CH, Ivanova T, Wu J, Lee M, Tan IB, Tao J, Ward L, Koo JH, Gopalakrishnan V, Zhu Y, Cheng LL, Lee J, Rha SY, Chung HC, Ganesan K, So J, Soo KC, Lim D, Chan WH, Wong WK, Bowtell D, Yeoh KG, Grabsch H, Boussioutas A, Tan P. Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer. PLoS Genet. 2009 Oct; 5(10).
LS Tham, L Wang, RA Soo, SC Lee, HS Lee, WP Yong, BC Goh, NHG Holford. A Pharmacodynamic Model for the Time Course of Tumor Shrinkage Associated with gemcitabine chemotherapy in Asian non-small cell lung cancer patients. Clin Cancer Res 2008; 14:4213-4218.