CSI PhD Student, Ms Wang Chao, from Dr Alan Prem Kumar’s group has recently won The Outstanding Poster Award at the 13th Asia Pacific Federation of Pharmacologist Meeting (APFP 2016) in Bangkok. Ms Wang Chao’s exceptional poster stood out amongst 208 poster presenters to receive this award reserved for best presentation.
The theme of the conference was “New Paradigms in Pharmacology for Global Health” and it aimed to provide different perspectives on the role of pharmacology in drug discovery and development research for important diseases. It also introduced the newest development and breakthroughs in pharmacology alongside other disciplines of drug discovery and development.
Ms Wang Chao’s research suggests that DDX20 can be used as a surrogate marker in Triple Negative Breast Cancer.
Congratulations to Ms Wang Chao!
DDX20 as a Surrogate Marker for Simvastatin Response in Triple Negative Breast Cancer
Chao Wang1,2, Beiying Qiu3, Jean Paul Thiery1,3,4,5, Patrick J. Casey6, Soo Chin Lee1,5,7, Celestial T. Yap5,8, Vinay Tergaonkar3,4, Alan Prem Kumar1,2,5,9,10
1Cancer Science Institute of Singapore, National University of Singapore
2Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore
3Institute of Molecular and Cell Biology (IMCB), ASTAR, Singapore
4Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore
5National University Cancer Institute of Singapore (NCIS), Singapore
6Duke-NUS Graduate Medical School, Singapore
7 Department of Haematology-Oncology, National University Hospital, Singapore
8Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
9School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia
10Department of Biological Sciences, University of North Texas, Denton, TX, USA
Simvastatin, a lipophilic statin used for lowering cholesterol, inhibits 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR), the key enzyme of the mevalonate pathway. Studies have shown that cancer cells express dysregulated level of HMGCR and statins exert anti-tumoral activities. Several clinical trials have reported simvastatin and other lipophilic statin-induced anti-proliferative effects in breast cancer. DDX20 is an RNA helicase involved in many cellular processes, and our group has recently identified it as a potential oncogene, promoting proliferation and metastasis in triple negative breast cancers (TNBCs). Interest is increasing rapidly in the use of surrogate markers as primary measures of the effectiveness of investigational drugs in clinical trials. In this study, we aim to investigate if DDX20, highly expressed in TNBCs, could serve as a surrogate marker for simvastatin treatment response. A correlation between 17 genes of the mevalonate pathway and DDX20 expression was assessed in a cohort of 1325 breast cancer tumors, with result showing that HMGCR has the highest positive correlation. Our following in vitro study showed TNBC are more responsive to simvastatin treatment compared to cells of other molecular subtypes. Exposure of TNBC cells, MDA-MB-231, to simvastatin resulted in DDX20 downregulation in a Rho-dependent manner. Conversely, forced expression of DDX20 abrogated the anti-metastatic activity of simvastatin. A similar result was observed in the mouse model, where simvastatin-treated mice showed significantly fewer visible lung metastases compared to placebo group. Immunohistochemical (IHC) staining on these lung tissues showed a decrease in DDX20 expression in simvastatin-treated group, corroborating our observations in vitro. Overall, our study suggests DDX20 is a potential surrogate marker for simvastatin treatment response in breast cancers and a long term implication of our findings is the possibility of an effective combinatorial therapeutic intervention using simvastatin (to suppress DDX20 gene expression) and a suitable first-line agent to treat invasive breast cancer.