New molecular test kit predicts patient’s survival and drug response
Singapore, August 1, 2014 – Researchers and doctors at the Institute of Bioengineering and Nanotechnology (IBN), Singapore General Hospital (SGH) and National Cancer Centre Singapore (NCCS) have co-developed the first molecular test kit that can predict treatment and survival outcomes in kidney cancer patients. This breakthrough was recently reported in European Urology, the world’s top urology journal.
According to IBN Executive Director Professor Jackie Y. Ying, “By combining our expertise in molecular diagnostics and cancer research, we have developed the first genetic test to help doctors prescribe the appropriate treatment for kidney cancer patients based on their tumor profile.”
Dr. Min-Han Tan, who is IBN Team Leader and Principal Research Scientist and a visiting consultant at the Division of Medical Oncology NCCS, shared his motivation, “As a practicing oncologist, I have cared for many patients with kidney cancer. I see the high costs of cancer care, the unpredictable outcomes and occasional futility of even the best available drugs. This experience inspired our development of this assay to improve all these for patients.”
The study was conducted retrospectively with tissue samples collected from close to 280 clear cell renal cell carcinoma (ccRCC) patients who underwent surgery at SGH between 1999 and 2012.
“High quality tissue samples are crucial in achieving significant findings in biomedical research. As an Academic Medical Center, we wish to promote the translation of research into advances in healthcare and personalized medicine. The development of this test kit for patient care, utilizing the robust tissue archive that we have at SGH, is a good example of this,” said Professor Tan Puay Hoon, Head and Senior Consultant, Department of Pathology, SGH.
Kidney cancer is among the ten most frequent cancers affecting men in Singapore, according to The Singapore Cancer Registry (2009-2013). The most common type of kidney cancer is clear cell renal cell carcinoma. Treatment options include surgery, ablation or removal of the tumor, or targeted therapy to shrink or slow the growth of the cancer. The latter works by blocking the growth of new blood vessels (angiogenesis) or important proteins in cancer cells (tyrosine kinase) that nourish the tumors and help them survive.
According to Dr. Min-Han Tan, there are currently about 250 new patients diagnosed with kidney cancer per year in Singapore. “Outcomes can be very different. Some patients can be observed for years on end, some benefit from immediate treatment including surgery or targeted therapy, and for some patients, treatment can be futile. Experience is required in making the right judgment for patients. We hope our assay will play a role in helping that judgment.”
Targeted drugs are prescribed routinely for cancer patients. Revenues from anti-angiogenic drugs, such as Sutent® and NexavarTM, are estimated at several billion dollars annually.
Such drugs, however, are not only expensive but may cause side effects in patients, including fatigue, loss of appetite, nausea, diarrhea, pain, high blood pressure, bleeding and heart problems. Due to genetic variations, individual patients respond differently to these drugs and have different survival outcomes.
Pharmaceutical companies and academic institutions have invested heavily in seeking out tools and biomarkers to predict personalized outcomes with these therapies, and the development of a reliable anti-angiogenic predictor would be of significant interest to them.
Extensive molecular characterization of ccRCC by the team and other researchers worldwide in recent studies has suggested the existence of specific subtypes with different survival outcomes. The researchers therefore set out to discover reliable biomarkers that could improve the prognostic prediction, and identify patients who would be likely to benefit from one type of treatment.
For this purpose, the team designed a practical assay for studying/diagnosing real-world tumor samples from ccRCC patients. The assay was able to distinguish patients into groups of different survival and treatment outcomes. This is one of the first assays capable of predicting outcomes of anti-angiogenic therapy, a key goal for cancer care and industry.
Dr. Tan added, “Our diagnostic assay successfully classified ccRCC into groups correlating to different survival and treatment outcomes. This allows patients and doctors to make more educated choices in their treatment options. Additionally, the development of such assays in Singapore demonstrates the highest levels of research, care and expertise that are available to our patients here.”
This test has been validated at the Singapore General Hospital and National Cancer Centre Singapore.
1. Y. Choudhury, X. Wei, Y.-H. Chu, L. G. Ng, H. S. Tan, V. Koh, A. A. Thike, E. Poon, Q. S. Ng, C. K. Toh, R. Kanesvaran, P. H. Tan and M.-H. Tan, “A Multigene Assay Identifying Distinct Prognostic Subtypes of Clear Cell Renal Cell Carcinoma with Differential Response to Tyrosine Kinase Inhibition,” European Urology, (2014) DOI: 10.1016/j.eururo.2014.06.041.
Images Available on Request:
Figure 1: Some members of the research team (clockwise from bottom left): IBN Postdoctoral Fellows Dr. Yukti Choudhury and Dr. Xiaona Wei, SGH Dept. of Pathology, Head and Senior Consultant, Prof. Tan Puay Hoon, NCCS Consultant Dr. Ravindran Kanesvaran, IBN Team Leader and Principal Research Scientist Dr. Min-Han Tan.
Figure 2: CT scan with arrow indicating kidney tumor
Figure 3: Nephrectomy specimen showing a renal cell carcinoma composed of a tumor mass with yellowish and hemorrhagic areas (arrow).
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About the Institute of Bioengineering and Nanotechnology
Established in 2003, the Institute of Bioengineering and Nanotechnology (IBN) is the world’s first bioengineering and nanotechnology research institute. IBN’s mission is to conduct multidisciplinary research across science, engineering, and medicine for breakthroughs to improve healthcare and quality of life.
IBN’s research activities are focused in the following areas:
· Nanomedicine, where functionalized polymers, hydrogels and biologics are developed as therapeutics and carriers for the controlled release and targeted delivery of therapeutics to diseased cells and organs.
· Cell and Tissue Engineering, where biomimicking materials, stem cell technology, microfluidic systems and bioimaging tools are combined to develop novel approaches to regenerative medicine and artificial organs.
· Biodevices and Diagnostics, which involve nanotechnology and microfabricated platforms for high-throughput biomarker and drug screening, automated biologics synthesis, and rapid disease diagnosis.
· Green Chemistry and Energy, which encompass the green synthesis of chemicals and pharmaceuticals, catalytic conversion of biomass, utilization of carbon dioxide, and new nanocomposite materials for energy applications.
· More than 970 papers published in leading scientific journals
· Over 1,000 seminars and presentations at international conferences, including over 660 invited, keynote and plenary lectures
· Organized premier scientific meetings such as the International Conference on Bioengineering and Nanotechnology, Nano Today Conference, and the IBN International Symposium
Technological and Commercialization Impact
· Over 500 active patents and patent applications
· More than 80 licensed patents and patent applications
· 7 spin-off companies
· Over 150 active research collaborations with industrial, clinical and academic partners
Nurturing Future Research Talents
· Trained 107 PhD students
· More than 76,200 students and teachers from 290 local and overseas schools/universities have participated in IBN’s Youth Research Program
· Over 2,000 students and teachers have completed research attachments at IBN
For more information about IBN, please visit www.ibn.a-star.edu.sg.
About National Cancer Centre Singapore
National Cancer Centre Singapore (NCCS) provides a holistic and multidisciplinary approach to cancer treatment and patient care. We treat almost 70 per cent of the public sector oncology cases, and they are benefiting from the sub-specialization of our clinical oncologists. NCCS is also accredited by the US-based Joint Commission International for its quality patient care and safety.
To deliver among the best in cancer treatment and care, our clinicians work closely with our scientists who conduct robust cutting-edge clinical and translational research programmes which have been internationally recognised. NCCS strives to be a global leading cancer center, and shares its expertise and knowledge by offering training to local and overseas medical professionals.
About Singapore General Hospital
Singapore General Hospital (SGH), a member of Singapore Health Services, is the public sector's flagship hospital. Established in 1821, SGH is Singapore's largest acute tertiary hospital with 1,700 beds and national referral center offering a comprehensive range of 36 clinical specialties on its campus. Every year, about 1 million Singaporeans benefit from advanced medical care delivered by its 800 specialists. As an academic healthcare institution and the bedrock of medical education, SGH plays a key role in nurturing doctors, nurses and allied health professionals, and is committed to innovative translational and clinical research in her continual strive to provide the best care and outcomes to her patients.
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 catalyzing 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 www.a-star.edu.sg.