Novel Gene Predicts Both Breast Cancer Relapse and Response to Chemotherapy

Despite advancements in cancer treatment, breast cancer remains the most common cancer among Singapore women[1]. Thirty percent[2] 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.

[1] Top 10 cancers affecting Singapore women: http://bit.ly/VEg7F8 [2] Lancet 365:1687-1717, 2005 - Early Breast Cancer Trialists' Collaborative Group: Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence; 15-year survival: An overview of the randomised trials

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 Shin 1,2, Hui Sin Hay 1,2,3, Moon Hee Lee 4, Jen Nee Goh 1,3, Tuan Zea Tan 1, Yin Ping Sen 5, See Wee Lim 5, Einas M. Yousef 6, Hooi Tin Ong 7, Aye Aye Thike 8, Xiangjun Kong 9, Zhengsheng Wu 9, Earnest Mendoz 10, Wei Sun 10, Manuel Salto-Tellez 1,11,12, Chwee Teck Lim 10,13,14, Peter E. Lobie 1,3,15, Yoon Pin Lim 16, Celestial T. Yap 17,18, Qi Zeng 2,16, Gautam Sethi 1,3, Martin B. Lee 19, Patrick Tan 1,20,21, Boon Cher Goh 1,18,22, Lance D. Miller 23, Jean Paul Thiery 1,2,16,18, Tao Zhu 9, Louis Gaboury 6, Puay Hoon Tan 8, Kam Man Hui 7, George Wai-Cheong Yip 5, Shigeki Miyamoto 4, Alan Prem Kumar 1,3,18,24,25, Vinay Tergaonkar 2,16.

1 Cancer Science Institute of Singapore, National University of Singapore, Singapore 2 Institute of Molecular and Cellular Biology, A*Star, Singapore Departments of 3 Pharmacology, 5 Anatomy, 11 Pathology, 16 Biochemistry, and 17 Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 4 McArdle Laboratory for Cancer Research, Department of Oncology, University of Wisconsin-Madison, Wisconsin, USA 6 Institute for research in immunology and cancer (IRIC), University of Montreal, Quebec, Canada 7 Division of Cellular and Molecular Research, Humphrey Oei Institute of Cancer Research, National Cancer Centre, Singapore 8 Department of Pathology, Singapore General Hospital, Singapore 9 Hefei National Laboratory for Physical Sciences at Microscale and School of Life Sciences, University of Science and Technology of China, Hefei, Anhui, P.R. China 10 Division of Bioengineering and Department of Mechanical Engineering, National University of Singapore, Singapore 12 Centre for Cancer Research and Cell Biology, Queen's University Belfast, United Kingdom 13 Mechanobiology Institute, National University of Singapore, Singapore 14 NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, Singapore 15 Liggins Institute, University of Auckland, New Zealand 18 National University Cancer Institute, Singapore 19 Renal Center, National University Hospital, Singapore 20 Cancer and Stem Cell Biology, Duke-NUS Graduate Medical School, Singapore 21 Genome Institute of Singapore, A*Star, Singapore 22 Department of Haematology-Oncology, National University Hospital, Singapore 23 Department of Cancer Biology, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA 24 School of Biomedical Sciences, Faculty of Health Sciences, Curtin University, Western Australia 25 Department 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

View post:

Novel Gene Predicts Both Breast Cancer Relapse and Response to Chemotherapy