The major focus of Dr Lee Soo Chin’s laboratory is to study pharmacogenetics and genomics in breast cancer. Using the neoadjuvant model, she has completed several clinical studies with collection of biological samples, including germline DNA, tumor and plasma, and conducted immunohistochemistry, genomic and proteomic studies to understand chemotherapy effects and to identify predictive markers of treatment response. She has also studied the pharmacogenetics of several commonly used chemotherapeutic agents in breast cancer, including doxorubicin, docetaxel and gemcitabine, and identified candidate gene variants that influence treatment toxicity and outcome. In addition, she has an interest in understanding inter-ethnic differences in drug outcomes between Asians and Caucasians and between different Asian races, and has studied the pharmacogenetics of warfarin and doxorubicin in relation to this. The goal of her research is to establish algorithms comprising key clinical and genetic predictors for optimal selection of anti-cancer drug for the individual patient.
Dr Lee Soo Chin’s laboratory is focused on pharmacogenetics and genomics in breast cancer to identify tumor and host genetic predictors for optimal selection of anti-cancer therapy for the individual patient. Traditionally, the baseline tumor is evaluated for prognostic and predictive biomarkers. However, a drug challenge may induce significant changes in the tumor and studying the post-treatment tumor sample could yield insights into mechanisms of drug resistance and uncover strategies to overcome them. For example, the laboratory studied expression changes of cyclo-oxygenase 2 (COX-2) in the tumor of breast cancer patients who were treated with doxorubicin and docetaxel chemotherapy, and found chemotherapy to down-regulate the expression of COX-2 predominantly in clinical responders. Estrogen receptor positive (ER+) and COX-2 positive tumours at baseline which remained COX-2 positive after chemotherapy fared worse than those which became COX-2 negative. This observed interaction between COX-2 and ER suggests that some hormone receptor positive patients whose tumors are COX-2 positive after receiving chemotherapy may benefit from combining COX-2 inhibition with hormonal therapy. For host pharmacogenetics, the laboratory recently studied UGT2B17 in relation to the pharmacokinetics and pharmacodynamics of vorinostat, a histone deacetylase inhibitor, in breast cancer patients. Patients who were homozygous for the UGT2B17 null variant (UGT2B17*2) glucuronidated vorinostat less efficiently and were exposed to higher vorinostat levels. In concordance, they experienced more serious adverse events but had higher clinical benefit rate and longer median progression-free survival than patients with at least one wild-type allele after vorinostat treatment. These observations are of particular relevance to the Asian population as the UGT2B17*2 genotype is common in Asians but rare in Caucasians, and may contribute to inter-ethnic differences in outcomes to other drugs that are metabolized by UGT2B17, such as exemestane and ibuprofen.
- Impact of UDP-gluconoryltransferase 2B17 genotype on vorinsotat metabolism and clinical outcomes in Asian breast cancer women. NS Wong, EZH Seah, LZ Wang, WL Yeo, HL Yap, B Chuah, YW Lim, PCS Ang, BC Tai, R Lim, BC Goh, SC Lee. Pharmacogenetics and Genomics 2011, Aug 17 (epub ahead of print)
- Serial changes in the expression of breast cancer-related proteins in response to neoadjuvant chemotherapy. BYS Chuah, T Putti, M Salto-Tellez, A Charlton, P Iau, SA Buhari, CI Wong, SH Tan, ALA Wong, CW Chan, BC Goh, SC Lee. Annals of Oncology 2011, 22(8); 1748-54
- Pharmacokinetics and pharmacodynamis of docetaxel with or without ketoconazole modulation in chemonaive breast cancer patients. YW Lim, BC Goh, LZ Wang, SH Tan, B Chuah, SE Lim, P Iau, SA Buhari, CW Chan, N Sukri, MT Cordero, R Soo, SC Lee. Annals of Oncol 2010, 21(11); 2175-82
- Phase III randomized trial of sunitnib versus capecitabine in patients with previously treated HER2-negative advanced breast cancer. CH Barrios, MC Liu, SC Lee, L Vanlemmens, J-M Ferrero, T Tabei, X Pivot H Iwata, K Aogi, R Lugo-Quintana, Na Harbeck, MJ Brickman, K Zhang, KA Kern, M Martin. Breast Cancer Research and Treatment 2010; 121(1): 121-31.
- Phase I and biomarker study of ABT-869, a multiple receptor tyrosine kinase inhibitor, in patients with refractory solid malignancies. CI wong, TS Koh, R Soo, S Hartono, CH Thng, E McKeegan, WP Yong, CS Chen, SC Lee, J Wong, R Lim, N Sukri, SE Lim, AB Ong, J Steinberg, N Gupta, R Pradhan, R Humerickhouse, BC Goh. J Clin Oncol 2009, 27(28); 4718-26
- Chemotherapy-induced tumor gene expression changes in human breast cancers. SC Lee, X Xu, YW Lim, P Iau, N Sukri, SE Lim, HL Yap, WL Yeo, P Tan, SH Tan, H McLeod, BC Goh. Pharmacogenetics and Genomics, 2009, 19: 181-92
- Pharmacogenetics in Breast Cancer Therapy. SH Tan, SC Lee, BC Goh, J Wong. Clin Cancer Research 2008, 14(24): 8027-41
- Genotype of human carbonyl reductase CBR3 correlates with doxorubicin disposition and toxicity. L Fan, BC Goh, CI Wong, N Sukri, SE Lim, SH Tan, JY Guo, R Lim, HL Yap, YM Khoo, P Iau, HS Lee,SC Lee. Pharmacogenetics and genomics 2008, 18(7): 623-31
- Inter-ethnic variability in warfarin requirement is explained by VKORC1 genotype in an Asian population. SC Lee, SS Ng, J Oldenburg, PY Chong, S Rost, JY Guo, HL Yap, SC Rankin, HB Khor, TC Yeo, KS Ng, R Soong, BC Goh. Clinical Pharmacology & Therapeutics 2006, 79(3): 197-205
- Explaining inter-individual variability of pharmacokinetics and pharmacodynacmis in Asians through genotyping and phenotyping strategies. BC Goh, SC Lee, LZ Wang, L Fan, JY Guo, E Schuetz, R Lim, HL Lim, AB Ong, HS Lee. J Clin Oncol, 20(17): 3683-90, 2002
|Name||LEE Soo Chin|
|Affiliations||Senior Principal Investigator, Cancer Science Institute of Singapore, NUS
Head and Senior Consultant, Department of Hematology/Oncology, NUHS
|Institute||Degree (if applicable)||Year(s)|
|National University of Singapore||MBBS||1992|
|National University of Singapore||M. Med (Internal Medicine)||1996|
|Royal College of Physicians, United Kingdom||MRCP||1996|
|Royal College of Physicians of Edinburgh||FRCP||2011|
|•||Senior Principal Investigator, Cancer Science Institute of Singapore, National University of Singapore||2009 – Present|
|•||Assistant Director of Research, National University Cancer Institute, Singapore||2009 – Present|
|•||Chairperson, Chapter of Medical Oncologists, Academy of Medicine||2009 – 2011|
|•||Chairperson, NHG, Domain-Specific Research Ethics Review Board B||2008 – Present|
|•||Member, NHG Executive Research Ethics Committee||2008 – Present|
|•||Member, Specialist Accreditation Board, Research Committee Selection,||2007 – Present|
|•||Training and Assessment Panel (Medical Specialties), Health Sciences Authority Pharmacogenetics Advisory Committee||2008 – Present|
Understanding the molecular mechanisms that contribute to the development and progression of different breast cancer subtypes. In addition, discovering the use of novel drugs in combination with current standard treatments to tailor treatment for the different breast cancer subtypes.
TAN Kee Mee