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First ever kidney cancer molecular test predicts patient’s survival and drug response.

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 is the first genetic test to help doctors prescribe the appropriate treatment for kidney cancer patients based on their tumour profile.  This breakthrough was recently reported in European Urology.

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 tumour, 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 tumours and help them survive.

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.

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. The team hope that their assay will play a role in helping that judgment.

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.

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.

For this purpose, the team designed a practical assay for studying/diagnosing real-world tumour 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.

The 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 patients.

This test has been validated at the Singapore General Hospital and National Cancer Centre Singapore.

Source:  Agency for Science, Technology and Research (A*STAR)

Coloured urogram (X-ray) of the left kidney of a patient with renal clear cell carcinoma (blue).  Credit: Sovereign, ISM/Science Photo Library
Coloured urogram (X-ray) of the left kidney of a patient with renal clear cell carcinoma (blue). Credit: Sovereign, ISM/Science Photo Library

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