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Cancer Solutions in Singapore

20150329-8

These are CT scans for two people found to have a left kidney tumor. The patient on the left has a poorly defined mass (radiologists typically describe it as infiltrative) while the one has the right has a well defined solid tumor. The tumor on the left was biopsied and found to be lymphoma. Johns Hopkins Website

 

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 1) ___cancer patients. This breakthrough was reported in European Urology. According to IBN Executive Director Professor Jackie Y. Ying, “By combining our expertise in molecular diagnostics and cancer research, we have developed the first 2) ___ test to help doctors prescribe the appropriate treatment for kidney cancer patients based on their tumor profile.“ The study was conducted retrospectively with tissue 3) ___collected from close to 280 clear cell renal cell carcinoma (ccRCC) patients who underwent surgery at SGH between 1999 and 2012. 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 4) ___. This experience inspired our development of this assay to improve all these for patients. 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 5) ___.“ 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 6) ___ 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 7) ___ 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 Nexavar, are estimated at several billion dollars annually. Such drugs, however, are not only expensive but may cause 8) ___ 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. As a result, 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 9) ___. 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 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. Source: A*STAR in Singapore; Yukti Choudhury, Xiaona Wei, Ying-Hsia Chu, Lay Guat Ng, Hui Shan Tan, Valerie Koh, Aye Aye Thike, Eileen Poon, Quan Sing Ng, Chee Keong Toh, Ravindran Kanesvaran, Puay Hoon Tan, Min-Han Tan. A Multigene Assay Identifying Distinct Prognostic Subtypes of Clear Cell Renal Cell Carcinoma with Differential Response to Tyrosine Kinase Inhibition. European Urology.

 

Singapore Researchers Identify Cells That Cause Gastric Cancer

 

10) ___cancer is a major cause of cancer-related deaths worldwide, with low survival and high recurrence rates for patients with advanced disease. New therapies for the treatment of gastric cancer are urgently needed.

 

A team of scientists led by a researcher from the Cancer Science Institute of Singapore (CSI Singapore) at the National University of Singapore has identified the cancer specific stem cell which causes gastric cancer. This discovery opens up the possibility of developing new drugs for the treatment of this disease and other types of cancers. The research group, led by Dr Chan Shing Leng, Research Assistant Professor at CSI Singapore, demonstrated for the first time that a cancer-specific variant of a cell surface protein, CD44v8-10, marks gastric cancer 11) ___cells but not normal cells. Conceptualized by Dr. Chan and Associate Professor Jimmy So, a Senior Consultant from the Department of Surgery at the National University Hospital Singapore, the study is also the first to be conducted with human gastric tissue specimens and took five years to complete. This novel study was published in the research journal Cancer Research.

 

How CD44v8-10 serves as a biomarker: Many cancer cell types express high levels of a cell surface protein known as CD44. This protein marks cancer stem cells that are thought to be responsible for resistance to current cancer therapy and tumor relapse. There are many forms of CD44 and the standard form of CD44, CD44s, is found in high abundance on normal blood cells. It was previously not known which form of CD44 is found on cancer stem 12) ___. This is critical as an ideal cancer target should mark only cancer cells but not normal cells. Research in the field has led to the hypothesis that the growth of gastric cancer may be driven by cancer stem cells. In this study, the researchers analyzed 53 patient tissue samples in conjunction with patient-derived xenograft models which are derived from intestinal type gastric cancer. The team is one of the few groups in the world to have a relatively large collection of patient-derived xenograft models for gastric cancer and the first to use these models for identification of gastric cancer stem cells. A total of eight cancer cell lines were used in this study, including six new cell lines which were established. The team discovered a cancer-specific CD44 variant, CD44v8-10 marks gastric cancer stem cells but not normal cells. CD44v8-10 promotes cancer cell growth and it is significantly more abundant in gastric tumor sites compared to normal gastric tissue, which makes it easily detectable. The findings results suggest that CD44v8-10 is an ideal target for developing clinical therapeutics against gastric cancer stem cells. As CD44v8-10 is cancer specific, it may also be used as a biomarker for screening and diagnosis of gastric cancer. This is significant as biomarkers for early detection of gastric cancer are currently not available and doctors rely on 13) ___ for the screening and diagnosis of this disease. Said Dr Chan, “With our findings, we can now work on developing drugs that would recognize and attack the cancer stem cells only, reducing the side effects on normal cells. With additional funding, we aim to have a drug that can show efficacy in our models within three years.“ “We are very excited about this discovery. It may explain why gastric cancer patients develop cancer relapse after chemotherapy as conventional chemotherapy mainly targets the common cancer cells. Hence, if we can find drugs that can target these gastric cancer stem cells, we may improve the patients’ outcome in the future,“ said Assoc Prof So, who is also a faculty member from the Department of Surgery at the NUS Yong Loo Lin School of Medicine. In the next phase of their research, the team aim to develop an antibody drug that targets CD44v8-10. The research team also hopes to establish more patient-derived xenograft models to achieve extensive coverage of the patient spectrum in Singapore as the level of CD44v8-10 varies among patients. These xenograft models play an important role as pre-clinical models for evaluating potential therapeutics that target CD44v8-10. Source: National University of Singapore; W. M. Lau, E. Teng, H. S. Chong, K. A. P. Lopez, A. Y. L. Tay, M. Salto-Tellez, A. Shabbir, J. B. Y. So, S. L. Chan. CD44v8-10 Is a Cancer-Specific Marker for Gastric Cancer Stem Cells. Cancer Research

 

Singapore Study Reduces Toxicities Metastatic Renal Cell Carcinoma: A study led by the Genitourinary (GU) oncology team at National Cancer Centre Singapore (NCCS) has revealed conclusive results in reducing toxicities for Asian patients with metastatic renal cell carcinoma (mRCC) or cancer that has spread beyond the kidney. The seven-year study began in 2007 and the findings revolutionized the standard protocol for patient management in NCCS with an attenuated-dose regimen of sunitinib (Sutent) for patients with mRCC. The new treatment regimen for sunitinib has been accepted by oncologists in Singapore. For the patients, this would mean an estimated 30% reduction in fees because of the lower dosage. The median overall survival rate was 27.4 as compared to 21.8 months among patients receiving the attenuated dosage. Sunitinib was introduced as a treatment for mRCC in Singapore since early 2005. The U.S. FDA approved dosing of sunitinib is 50mg once daily for four weeks, followed by a two-week break in a six-week treatment cycle (conventional-dose regimen). Subsequent findings from 2005 to 2006 show that high toxicities were observed with the conventional dosing, especially in Asians. “Many of the patients were experiencing severe side effects of grade 3 or higher with the conventional dosing. Our immediate response was to refine the treatment protocol to improve patients’ quality of 14) ___,“ explained Dr Tan Min Han, Visiting Consultant, Division of Medical Oncology and member of the GU team, NCCS. NCCS initiated a prospective clinical registry with 127 mRCC patients receiving attenuated sunitinib dosing of 37.5mg/d/4/2 (37.5mg of sunitinib once daily for four weeks, followed by a two-2 week break) as treatment protocol in 2007. Clinical data of patients receiving sunitinib at NCCS from 2005 to 2012 and three other tertiary centres in Singapore (Johns Hopkins-International Medical Centre, National University Hospital Singapore, and Onco-Care of Gleneagles Medical Centre) from 2005 to 2009 were used for comparison, representing at least 90% of all patients with mRCC treated over the period. The data revealed favorable results between the attenuated dosing regimen compared to the conventional dosing. 59% of the participants experienced severe side effects as compared to the previous 85%; 24% than 58% required reduction in dose delays; and 35% rather than 70% of patients requiring dose reduction during their course of treatment. Both dose delays and reduction are only required when high level of toxicities are observed. Dr Tan reiterated the importance of the findings, “This is an affirmation to our efforts and we believed that the continuous understanding of real world outcomes will reap greater benefits for our patients. The findings would not be possible without the collaborative nature of our tertiary healthcare counterparts.“ Source: SingHealth; Hui Shan Tan, Huihua Li, Yu Wen Hong, Chee-Keong Toh, Alvin Wong, Gilberto Lopes, Miah Hiang Tay, Alexandre Chan, Xin Yao, Tiffany Tang, Quan Sing Ng, Ravindran Kanesvaran, Noan Minh Chau, Min-Han Tan. Efficacy and Safety of an Attenuated-Dose Sunitinib Regimen in Metastatic Renal Cell Carcinoma: Results From a Prospective Registry in Singapore. Clinical Genitourinary Cancer

 

ANSWERS: 1) kidney; 2) genetic; 3) samples; 4) drugs; 5) medicine; 6) cancer; 7) blood; 8) side; 9) treatment; 10) Gastric; 11) stem; 12) cells; 13) endoscopy; 14) life

 

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