Urinary exosome test for improved prostate cancer management

Researchers at Oslo University Hospital have shown that the levels of many protein biomarkers in extracellular vesicles isolated from urine differ between cancer and healthy individuals, and that these proteins could form the basis of a prostate cancer test of high diagnostic accuracy. We have evaluated two different analysis platforms and chosen MS as platform of choice for further validation. Urine samples from prostate cancer patients with different grade of disease as well as other urinary tract cancers and healthy individuals have been collected and analyzed to determine the optimal product marker composition and primary clinical utility. Based on an analysis of collected clinical samples and a review of unmet medical need, we identified pre-diagnostic support for the decision on whether to perform a biopsy as primary clinical utility. There are several strong companies that work on the development of novel tests for prostate cancer treatment based on urinary analyses. This activity from (competing) companies form create a higher threshold for market entrance for a new product, but also underline the general comemrcial potential for novel products facilitating prostate cancer treatment decisions. The project has been focused on strengthening the basis for product definition and provide more accurate estimates on diagnostic accuracy within the chosen clinical utility. We also worked on evaluating how various methods for storage and processing of urine samples before MS analysis affected the performance of the test. We evaluated several potential markers and conclude that, based on the currently available data and technology, it remains a challenge to define an optimal robust multi-marker set and a prototype product with a sufficeint level of robustness.

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Prostate cancer is a global health problem, with an estimated 1.1 million new cases worldwide in 2012. The two main challenges of prostate cancer management are improving the accuracy of early diagnosis, and to differentiate between patients with a clinically significant cancer requiring treatment and those with indolent cancers that are unlikely to progress. Prostate specific antigen (PSA) has been used for nearly three decades as a biomarker for prostate cancer, but has poor sensitivity and specificity, and does not give information about cancer aggressiveness. The development of additional biomarkers to supplement PSA is therefore strongly needed, and is reflected by the strong activity among biotech industry in this field. We have used mass spectrometry to identify potential prostate cancer biomarkers in exosomes from urine samples, comparing the proteomes of prostate cancer patients and healthy individuals. The most diagnostically promising marker exhibited sensitivity of 94% at 100% specificity, while additional 16 markers had individual sensitivities above 60%. Our literature searches indicate that the majority of the leading candidate biomarkers, have not been associated with prostate cancer exosomes. Combination of selected biomarkers in panels of as few as two biomarkers was sufficient to provide full sensitivity. Incorporation of additional markers in a multi-marker panel is expected to improve diagnostic accuracy and robustness of a test. We now seek to transfer the biomarkers to an immunoassay format, which is more amenable to routine clinical practice, define the optimal composition of a prototype multi-marker test, and identify and provide clinical validation for the primary clinical utility of the test. Successful completion of this project is expected to allow us to commercialize the innovation, through either partnering with an established international molecular diagnostics company or establish a new company for further development.