Research is viewed as an essential requirement for all clinical staff in the department. The Department of Haematology-Oncology has focused its research efforts in the following areas:
- Experimental therapeutics including phase I and II clinical trials, especially for tumours that are endemic in the Asian population like hepatocellular and nasopharyngeal cancers.
- Pharmacogenomics to explain ethnic variation of drug response and toxicity.
- Cancer genetics to elucidate the genetic basis for inherited cancers in the Asian population.
The flagship program in the department is the clinical trial collaboration between NUH/ NUS, JHS, NCC, CUHK and SCC called the Cancer Therapeutics Research Group (CTRG).
THE CANCER THERAPEUTICS RESEARCH GROUP (CTRG)
The Cancer Therapeutics Research Group was founded in SIngapore in 1997 to address the need for high quality clinical research for antineoplastic drug development in Asians, define the differences in drug pharmacokinetics and pharmacodynamics between Asians and Caucasians, and provide platform for translational research.
The CTRG has succeeded in forging strong collaborations between prestigious institutions like Sydney Cancer Centre, Johns Hopkins SIngapore, Chinese University HongKong and the National Cancer Centre Singapore. Through this, we have attracted large pharmaceutical corporations to the region to conduct clinical research and development, and have established a reputation for early phase clinical trials in South East Asia and the Asia Pacific. We have also collaborated with the National Cancer Institute of the USA inevaluation of promising compounds identified by the NCI.
For NUH, the CTRG has been able to attract significant research funding from the Biomedical Research Council of Singapore. The funding has brought in research nursing manpower, trained clinical research associates,administrative support for the clinical trial infrastructure. If we realise that these are people involved in the day-to day care of patients of the hospital, it becomes clear that the CTRG actually does clinical work for
NUH. Pivotal studies of novel anticancer drugs have been initiated, and have attracted foreign patients to NUH (from as far as Israel). This has brought substantial revenue for NUH, and highlighted NUH as a tertiary centre where cutting edge treatments are available. At the CTRG, our objective is to enhance the global visibility of NUH, Singapore and South East Asia as a centre for cancer clinical research.
For more information on CTRG, go to www.ctrg.org.
Clinical Trials
Our clinical trials infrastructure consists of a team of 6 research nurses/data managers, 2 administrators, and 10 fully trained clinical investigators. Pharmacy support is from the Cancer Centre Pharmacy. Over the past 5 years, we have built up a comprehensive portfolio of clinical trials including phase I, II and III studies, both investigator initiated and industry sponsored. The results of completed trials have been published, presented at research meetings or in data analysis.
Pharmacogenetics/pharmacogenomics
Another important research program in the department is in the field of pharmacogenomics of anticancer drugs. With the completion of human genome sequencing, it has been recognized that numerous genetic polymorphisms exist, and can impact on protein functions. Our work involves identifying these genetic polymorphisms, and to link these to the drug behaviour in patients. The work has great pertinence in oncology as cytotoxics have narrow therapeutic windows, and differences in drug metabolism exist between ethnic populations. This has the potential to allow individualization of drug treatment and dosing. The department has secured a programmatic grant from the Agency for Science, Technology and Research (A*STAR) to conduct these studies.
Cancer Genetics
Differences in cancer epidemiology exist between Asian populations and Western populations. Several tumours are endemic in Asia and not in Western countries. Hereditary cancer predisposition genes may be different in the Asian population; therefore current risk assessment models may not be applicable to our population. Therefore, the Department has established a cancer genetic clinic, as well as a research program aimed at defining the common genetic defects that predispose an individual to cancer development.
ONGOING PROJECTS
Investigation of gene expression patterns of non-small cell lung carcinoma (NSCLC) in our local population using low-volume tissue samples and microarray analysis
- Dr Elaine Lim
Characterization of CYP3A4 Genotype & Phenotype in the Singaporean (SEA) Population & Correlation with Docetaxel Pharmacokinetics Pharmacodynamics
- Dr Goh Boon Cher
Characterization of CYP3A4 Genotype & Phenotype in the Singaporean (SEA) Population & Correlation with Docetaxel Pharmacokinetics Pharmacodynamics
- Dr Goh Boon Cher
Characterization of CYP3A4 Genotype & Phenotype in the Singaporean (SEA) Population & Correlation with Docetaxel Pharmacokinetics Pharmacodynamics
- Dr Goh Boon Cher
Study of Genetic Predisposition to Chemotherapy related toxicity
- Dr Robert Lim
A clinical study of cyclooxygenase-2 inhibition on its relevant downstream molecular pathways in undifferentiated nasopharyngeal carcinoma
- Dr Ross Soo
A Phase 1 Study of Docetaxel with Ketoconazole Modulation in Solid Tumours
- Dr Yong Wei Peng
Start-up funds for family history and DNA Bank
- Dr Lee Soo Chin
Prevalence of the I1307K Mutation in the Adenomatous Polyposis Coli Gene in Chinese Colorectal Cancer Patients in Singapore
- Dr Lee Soo Chin
Prevalence of Germline mutations in the hMLH1 and hMSH2 genes in Singaporean Colorectal Cancer Patient suspected Clinically to have Hereditary Non-Polyposis Colorectal Cancer and Corelation with Clinical and Family History & Tumour Status
- Dr Lee Soo Chin
Predicting the risk of breast cancer using family history: Validation of the Claus model in an Asian population
- Dr Lee Soo Chin
Projects of the Cancer Therapeutics Research Group
PUBLICATIONS (From Year 2000)
Chang J, Sng JH, Hilsenbeck SG, Wong J, Ragu GC.
Pathologic features and BRCA mutation screening in premenopausal breast cancer.
Clinical Cancer Research, 7 (June 2001):1739 - 1742.
Goh BC, Fleming GF, Janish L, Vogelzang NJ, Stadler WM, Ratain MJ.
Development of a schedule independent pharmacodynamic model for rhizoxin without plasma concentrations.
Cancer Chemother Pharmacol, 45 no.6 (2000):489-494.
Goh BC, Lehnert ML, Lim HL, Ng A, Chan CC, Kong HL, et al.
Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer.
Acta Oncologica, 39 no.2 (2000): 225-229
Goh BC.
Design of phase I and II clinical trials in oncology and ethical issues involved.
Ann Acad Med Singapore, 29 (2000):588-597.
Goh BC, Ratain MJ, Smith R, Bertucci D, Mani S, Vogelzang NJ, et al.
Phase I study of ZD9331 using a 5-day short infusion schedule.
J Clin Oncol 19 (2001) :1476-1484
Goh BC, Vokes EE, Amita Joshi, Ratain MJ
Phase I study of the combination of losoxantrone and cyclophosphamide in patients with refractory solid tumors.
Br J Cancer 2002 (in press).
Goh BC, Lee HS, Lee SC, Wang LZ., Fan L, Cai J, Lim R, Ong AB
Interindividual Variability of Docetaxel Pharmacokinetics (PK) correlates with Midazolam Phenotyping but not genotype of the regulatory region of CYP3A4 in Asian Patients.
(In press)
Goh BC, Lehnert M, Lim HL, Ng AW, Chan CC, Kong HL, SC Lee, Wee J, Chua ET, Wong JE.
Phase II trial of docetaxel in Asian patients with inoperable stage III non-small cell lung cancer. Acta Oncol;39 no.2 (2000):225-9
Kong HL, Boyer MJ, Lim R, Clarke S, Millward MJ, Wong JE
Phase II trial of thalidomide in unresectable hepatocellular carcinoma (HCC) - a Cancer Therapeutics Research Group (CTRG) study.
Proceedings of American Society of Clinical Oncology (ASCO), 20 (2001).
Kong HL, Wong JEL, Zhang J, Wong CMY, Bodnar A, Tan Y, Wong MC
Antiangiogenesis gene therapy: Effective suppression of metastatic tumors using soluble flt-1 cDNA mediated by adenoviral gene vector. Experimental and Clinical Regulation of Angiogenesis (D2), Keystone Symposia, March 2 - 7, 2000, Salt Lake City, Utah
Lee SC, Bernhardt BA, HelzlsoueKJ
Utilization of BRCA1/2 genetic testing in the clinical setting: report from a single institution. Cancer 2002.
Lee SC, Berg KD, Sherman ME, Griffin CA, Eshleman JR
Microsatellite instability is infrequent in medullary breast cancer. Am J Clin Path (2001): 115-823
Lee SC, Berg KD, Racke FK, Griffin CA, Eshleman JR
'Pseudo-spikes' are common in histologically benign lymphoid tissues. J Molecular Diagnostics, 2 (2000):145-152
Lee SC, Wong JEL, Kueh YK.
Clinical characteristics and treatment outcome of 218 patients with non-Hodgkin's lymphoma in a Singaporean institution. Singapore Med J, 41 no. 2 (2000):77-79
Soo R, Motum P and Pokorny CS.
How to Investigate the Patient who is Hypercoagulable. Medical Progress, January (2000): 37-40
Yong Wei Peng, Chua Charlotte, Lim Siew Eng.
Analysis of Breast Ductal Carcinoma In Situ (DCIS) in Asian Women Suggests an Earlier Age Of Clinical Presentation. Proceeding of ASCO Vol. 20 (2001):1905 p39b.
Wong Seng Weng, Yong Wei Peng, Paul Ananth Tambyah, Lim Siew Eng.
Prospective Analysis of Clinical Outcomes and Pattern of Care of Neutropenic Patients with Fever. 5th NUH-NUS Faculty of Medicine Annual Scientific Meeting. Vol. 5, 2001:86 p125
CONTACT INFORMATION
| Name |
Dr Lim Hong Liang |
| Designation |
Chief |
| Department |
Department of Haematology-Oncology |
| Address |
National University Hospital
5 Lower Kent Ridge Road
Singapore 119074
|
| Telephone |
(65) 67724140 |
| Fax |
(65) 67775545 |
| Email |
LimHL@nuh.com.sg |
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