Singapore—Scientists have made it easier to predict both breast cancer relapses and responses to chemotherapy, through the identification of a unique gene. The newly found marker could help doctors classify each breast cancer patient and customise a treatment regimen that is more effective. The discovery was a collaborative effort by scientists from A*STAR's Institute of Molecular and Cell Biology (IMCB), and the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore (NUS).
Despite advancements in cancer treatment, breast cancer remains the most common cancer among Singapore women . Thirty percent of early breast cancer patients in the world experience relapse due to metastasis, or the spread of cancer cells to other organs in the body. Some patients also do not respond well to chemotherapy. The inability to forecast relapses or the effectiveness of chemotherapy has led to a pressing need to identify predictive markers, which doctors can use to tailor appropriate treatment for each breast cancer patient at an early stage.
In a study published recently in the Journal of Clinical Investigation, a top-tier journal for discoveries in basic and clinical biomedical research, the team of scientists jointly led by Dr Vinay Tergaonkar, Principal Investigator at IMCB and Dr Alan Prem Kumar, Principal Associate at CSI Singapore and Assistant Professor at the Department of Pharmacology, NUS Yong Loo Lin School of Medicine, uncovered a gene, DP103, which is activated in metastatic breast cancer. DP103 acts as a master regulator, which expresses two sets of unfavourable proteins – one leads to metastasis and the other causes patients to be unresponsive to chemotherapy. Consequently, doctors can predict the probability of metastasis by examining the levels of DP103 in breast cancer patients. The same gene could also be used to predict whether a patient would respond to chemotherapy.
"Doctors are unable to tell if a breast cancer patient will respond to chemotherapy until six months after the treatment has been prescribed. It is very worrisome as the ones who are not responsive to chemotherapy usually also suffer relapses due to metastasis. This DP103 gene that we found explains the link and will facilitate doctors in selecting suitable treatments for different cases of breast cancer," said Dr Tergaonkar.
In addition, the study revealed that reducing the levels of DP103 could contain the cancer, shrink the tumour and make patients more amenable to chemotherapy. All the findings in the study have been validated with samples of breast cancer patients from Singapore, Canada, China and the USA.
"DP103 is a novel biomarker that could help doctors select appropriate treatments for breast cancer patients at an early stage. It is also a therapeutic target which could be explored further to develop drugs that suppress breast cancer growth, as well as metastasis," said Dr Kumar, who first discovered DP103's oncogene potential to drive breast cancer metastasis. He is also the Principal Inventor to a patent application on this discovery and is currently looking into ways to regulate DP103 levels in a variety of cancer types at CSI Singapore.
Figure 1: Difference in DP103 (red) levels in a healthy person (left image) and a breast cancer patient (right image)
Notes to Editor:
The research findings described in this media release can be found in the Journal of Clinical Investigation Journal, under the title, "DEAD-box Helicase DP103 Defines Metastatic Potential of Human Breast Cancers" by Eun Myoung Shin1,2, Hui Sin Hay1,2,3, Moon Hee Lee4, Jen Nee Goh1,3, Tuan Zea Tan1, Yin Ping Sen5, See Wee Lim5, Einas M. Yousef6, Hooi Tin Ong7, Aye Aye Thike8, Xiangjun Kong9, Zhengsheng Wu9, Earnest Mendoz10, Wei Sun10, Manuel Salto-Tellez1,11,12, Chwee Teck Lim10,13,14, Peter E. Lobie1,3,15, Yoon Pin Lim16, Celestial T. Yap17,18, Qi Zeng2,16, Gautam Sethi1,3, Martin B. Lee19, Patrick Tan1,20,21, Boon Cher Goh1,18,22, Lance D. Miller23, Jean Paul Thiery1,2,16,18, Tao Zhu9, Louis Gaboury6, Puay Hoon Tan8, Kam Man Hui7, George Wai-Cheong Yip5, Shigeki Miyamoto4, Alan Prem Kumar1,3,18,24,25, Vinay Tergaonkar2,16
1Cancer Science Institute of Singapore, National University of Singapore, Singapore
2Institute of Molecular and Cellular Biology, A*Star, Singapore
Departments of 3Pharmacology, 5Anatomy, 11Pathology, 16Biochemistry, and 17Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
4McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Wisconsin, USA
6Institute for research in immunology and cancer (IRIC), University of Montreal, Québec, Canada
7Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore
8Department of Pathology, Singapore General Hospital, Singapore
9Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P.R. China
10Division of Bioengineering and Department of Mechanical Engineering, National University of Singapore, Singapore
12Centre for Cancer Research and Cell Biology, Queen's University Belfast, United Kingdom
13Mechanobiology Institute, National University of Singapore, Singapore
14NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore
15Liggins Institute, University of Auckland, New Zealand
18National University Cancer Institute, Singapore
19Renal Center, National University Hospital, Singapore
20Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore
21Genome Institute of Singapore, A*Star, Singapore
22Department of Haematology-Oncology, National University Hospital, Singapore 23Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA
24School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia
25Department of Biological Sciences, University of North Texas, Denton, Texas, USA.
Full text of the Journal of Clinical Investigation paper can be accessed online from: http://www.ncbi.nlm.nih.gov/pubmed/25083991
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About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is Singapore's lead public sector agency that fosters world-class scientific research and talent to drive economic growth and transform Singapore into a vibrant knowledge-based and innovation driven economy.
In line with its mission-oriented mandate, A*STAR spearheads research and development in fields that are essential to growing Singapore's manufacturing sector and catalysing new growth industries. A*STAR supports these economic clusters by providing intellectual, human and industrial capital to its partners in industry.
A*STAR oversees 18 biomedical sciences and physical sciences and engineering research entities, located in Biopolis and Fusionopolis, as well as their vicinity. These two R&D hubs house a bustling and diverse community of local and international research scientists and engineers from A*STAR's research entities as well as a growing number of corporate laboratories.
For more information on A*STAR, please visit http://www.a-star.edu.sg.
About the Institute of Molecular and Cell Biology (IMCB)
The Institute of Molecular and Cell Biology (IMCB) was launched on 23 January 1985, with its official opening ceremony held on 2 October 1987 at the National University of Singapore (NUS). It subsequently became an autonomous research institute (RI) of A*STAR, moving to Biopolis in 2004. IMCB's vision is to be a premier cell and molecular biology institute which addresses the mechanistic basis of human diseases and its mission is to conduct cutting-edge discovery research in disease pathways; to groom early career researchers to be future leaders in research; and to collaborate with medical and industry communities for research impact. IMCB plays an important role training and recruiting scientific talents, and has contributed to the development of other research entities in Singapore. Its success in fostering a biomedical research culture in Singapore has catalysed Singapore's transformation into an international hub for biomedical research, development and innovation.
Funded primarily by the Biomedical Research Council (BMRC) of A*STAR, IMCB's current discovery research includes cell biology in health and disease; animal models of development & disease; cancer & stem cell genetics & genomics; and structural biology & drug discovery. IMCB's translational research includes humanised model organisms for human diseases; systems approach for disease target identification & validation; and protein engineering & antibody development for diagnostics & therapeutics. Research activities in IMCB are supported by cutting edge infrastructure and facilities including quantitative proteomics; humanised mice; mouse models of human cancer; protein crystallography X-ray; zebrafish for drug metabolism & toxicology; advanced molecular histopathology; imaging & electron microscopy; and DNA sequencing.
For more information about IMCB, visit http://www.imcb.a-star.edu.sg
About National University of Singapore (NUS)
A leading global university centred in Asia, the National University of Singapore (NUS) is Singapore's flagship university, which offers a global approach to education and research, with a focus on Asian perspectives and expertise.
NUS has 16 faculties and schools across three campuses. Its transformative education includes a broad-based curriculum underscored by multi-disciplinary courses and cross-faculty enrichment. Over 37,000 students from 100 countries enrich the community with their diverse social and cultural perspectives.
NUS has three Research Centres of Excellence (RCE) and 24 university-level research institutes and centres. It is also a partner in Singapore's fifth RCE. NUS shares a close affiliation with 16 national-level research institutes and centres. Research activities are strategic and robust, and NUS is well-known for its research strengths in engineering, life sciences and biomedicine, social sciences and natural sciences. It also strives to create a supportive and innovative environment to promote creative enterprise within its community.
For more information, please visit http://www.nus.edu.sg
About Cancer Science Institute of Singapore
The Cancer Science Institute of Singapore (CSI Singapore) was officially launched on 15 October 2008. CSI Singapore aims to position Singapore as a global-leader in the field of Biomedical Sciences. Its mission: to conduct a multifaceted and coordinated approach to cancer research, extending from basic cancer studies all the way to experimental therapeutics and in so doing improve cancer treatment.
CSI Singapore is a state-of-the-art university research institute affiliated with, and hosted at the National University of Singapore. In 2008, it was awarded a $172 million "Research Center of Excellence" grant, one of only five in Singapore, by the National Research Foundation and the Ministry of Education. Professor Daniel G Tenen, MD, was named its founding director. Professor Tenen is a leader in the field of transcriptional regulation, hematopoiesis, and cancer.
The institute is an anchor for research expertise in two broad programs; Cancer Biology & Stem Cells, and Experimental Therapeutics; these programs form expansive platforms for CSI Singapore's focus on key cancer disease cancers in gastric, liver, lung and leukemia which are endemic in Asian populations.
For more information, please visit http://www.csi.nus.edu.sg/wp/
Journal
Journal of Clinical Investigation