With the molecular characteristics of cancers in guiding therapy gaining increasing attention, specific molecular abnormalities predict sensitivity to particular kinase inhibitors in lung cancers and chronic leukemia. In this project, Dr Hsieh seeks to (i) quantify the viral gene activation associated with several chemotherapy regimens and molecularly targeted agents, (ii) to characterize the time course of viral activation, (iii) to explore potential utility of viral gene activation for tumour imaging and (iv) to explore the tumour-selective targeting of radiopharmaceuticals in early phase clinical trials. This project will involve collaborations with clinicians and translational scientists from NUS/NUH, Singapore General Hospital and Johns Hopkins University School of Medicine.
Molecular characteristics of certain cancers have allowed specific targeting of genetic and epigenetic abnormalities in certain cancers such as lung cancer and chronic myelogenous leukemia. Our investigations are based on the premise that the presence of the EBV genome or tumor specific genetic and epigenetic abnormalities in nasopharyngeal carcinoma (NPC) may similarly identify tumors that can be specifically targeted. The viral genome is largely transcriptionally silent in these tumors but our investigations have suggested that pharmacologic activation of viral enzyme expression will allow selective targeting of radiopharmaceuticals to these tumors. We are developing targeted therapies for NPC via the induction of silenced Epstein-Barr virus (EBV) and cellular tumor suppressor gene (TSG) expression. Ongoing trials include those testing the clinical and biological effects of valproic acid and Azacitidine/SAHA by standard clinical criteria and molecular characterization of tumor and blood specimens.
In addition, we seek to quantify the viral gene activation associated with several chemotherapy regimens as well as molecularly targeted agents, to characterize the time course of viral activation, and to explore the potential utility of viral gene activation for tumor imaging and to explore the tumor selective targeting of radiopharmaceuticals in an early phase clinical trial.
We are also continuing to develop cell cycle inhibitors for the treatment of NPC. NPC has a number of aberrations in the regulators of the cell cycle. Our previous studies have shown that NPC tumors in vitro and in vivo are sensitive to the effects of cell cycle inhibition. We are currently engaged in preclinical evaluation of a novel cell cycle inhibitor and will proceed to early phase clinical trials once the pharmacodynamics modeling has been completed.
This project will form a part of the translational therapeutic component of CSI while collaborating with clinicians and translational scientists in NUS/NUH, Singapore General Hospital (SGH), and Johns Hopkins University School of Medicine.
- Low, SW, Tao, Q*, Ng, KM, Goh, HK, Shu, XS, Ambinder, RF, Srivastava, G, Shamay, M, Chan ATC, Popescu, NC, Hsieh, WS*. A novel isoform of the 8p22 tumor suppressor gene DLC1 suppresses tumor growth and is frequently silenced in multiple common tumors. Oncogene. 30(16): 1923-35. *Co-Corresponding Author.
- Hsieh, WS, Soo, RA, Peh, BK, Loh, T, Dong, DF, Soh, D, Wong, LS, Green, SR, Chiao, JT, 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. Clinical Cancer Research, 15;15(4):1435-42, 2009.
- Tan SH, Ida H, Goh BC, Hsieh WS, Loh M, Ito Y. Analyses of Promoter Hypermethylation for RUNX3 and Other Tumor Suppressor Genes in Nasopharyngeal Carcinoma. Anticancer Res. 2006 Nov-Dec; 26(6B): 4287-92.
- Soo RA, Wu J, Aggarwal A, Tao Q, Hsieh WS, Putti T, Tan KB, Low JS, Lai YF, Mow B, Hsu S, Loh KS, Tan L, Tan P, Goh BC. Celecoxib Induces Changes in Gene Expression and Reduces Microvessel Density in Patients with Nasopharyngeal Carcinoma. Ann Oncol. 2006 Nov; 17(11): 1625-30.
- Seng TJ, Low JS, Li H, Cui Y, Goh HK, Wong ML, Srivastava G, Sidransky D, Califano J, Steenbergen RD, Rha SY, Tan J, Hsieh WS, Ambinder RF, Lin X, Chan AT, Tao Q. The major 8p22 tumor suppressor DLC1 is silenced by methylation in both endemic and sporadic nasopharyngeal, esophageal and cervical carcinomas, and inhibits tumor cell colony formation. Oncogene. 2007 Feb 8; 26(6): 934-44.
- Wong AS, Soo RA, Lu JJ, Loh KS, Tan KS, Hsieh WS, Shakespeare TP, Chua ET, Lim HL, Goh BC. Paclitaxel, 5-fluorouracil and hydroxyurea concurrent with radiation in locally advanced nasopharyngeal carcinoma. Ann Oncol. 2006 Jul; 17(7): 1152-7.
- Lee SC, Lim SG, Soo R, Hsieh WS, Guo JY, Putti T, Tao Q, Soong R, Goh BC. Lack of Somatic Mutations in EGFR tyrosine kinase domain in Hepatocellular and Nasopharyngeal Carcinoma. Pharmacogenet Genomics. 2006 Jan; 16(1): 73-4.
- Ying J, Srivastava G, Hsieh WS, Gao Z, Murray P, Liao SK, Ambinder R and Tao Q. The stress-responsive gene GADD45G is a functional tumor suppressor, with its response to environmental stresses frequently disrupted epigenetically in multiple tumors. Clin Cancer Res. 2005 Sep 15; 11(18): 6442-9.
- Soo R, Putti T, Tao Q, Goh BC, Lee KH, Kwok-Seng L, Tan L, Hsieh WS. Overexpression of cyclooxygenase-2 in nasopharyngeal carcinoma and association with epidermal growth factor receptor expression. Arch Otolaryngol Head Neck Surg. 2005 Feb; 131(2): 147-52.
- Lee WH, Morton RA, Epstein JI, Brooks JD, Campbell PA, Bova GS, Hsieh WS, Isaacs WB, Nelson WG. Cytidine Methylation of Regulatory Sequences Near the Pi-Class Glutathione S-Transferase Gene Accompanies Human Prostatic Carcinogenesis. Proc Natl Acad Sci USA. 1994 Nov 22; 91(24): 11733-7.
|Affiliations||Principal Associate, Cancer Science Institute of Singapore, NUS
NUS Visiting Consultant, Department of Otolaryngology, NUH
|Institute||Degree (if applicable)||Year(s)|
|Tulane University, New Orleans, LA||B.S.||1988|
|The Johns Hopkins University School of Medicine, Baltimore, MD||M.D.||1994|
|•||Principal Associate, Cancer Science Institute of Singapore, National University of Singapore||Present|
|•||Medical Oncologist, Singapore Oncology Consultants||2011 – present|
|•||Adjunct Assistant Professor, Johns Hopkins University School of Medicine||2008 – present|
|•||Visiting Consultant, Department of Head and Neck Surgery National University Hospital||2008 – present|
|•||Consultant Medical Oncologist and Medical Director, International Cancer Specialists||2008 – 2011|
|•||Assistant Professor, Johns Hopkins University School of Medicine||2001 – 2008|
|•||Consultant in Oncology, Johns Hopkins-National University Hospital-IMC||2001 – 2008|
|•||Investigator, Cancer Epigenetics and Tumor Virology Laboratory, Johns Hopkins Singapore||2001 – 2006|
|•||Visiting Consultant, Department of Hematology/Oncology, NUH, Singapore||2002 – 2005|
|•||Principal Investigator, Oncology Therapeutics Laboratory, Div of Biomedical Sciences, Johns Hopkins S’pore||2005 – 2006|