Breakthrough could lead to new prostate cancer test

A newly discovered molecule linked to aggressive prostate cancer could open the door to better ways of tracking and treating the disease, say scientists.

The biomarker, called sarcosine, appears to help cancer spread out from the prostate gland and invade other parts of the body.



Since it is found in urine, the molecule could allow aggressive and spreading prostate cancer to be diagnosed with a simple "pee test".



Early research indicates that it could also provide a new avenue for drug treatment.



Prostate cancer affects around 35.000 men each year in the UK, resulting in some 10,000 deaths.



But there is a marked difference between aggressive prostate cancers - known as "tigers" - and slow-growing "pussycat" tumours.



Knowing whether a cancer is fast or slow growing has important implications for treatment.



Depending on a man's age, a slow-growing cancer can often be left alone and simply monitored, because the patient might well die from other causes before it becomes dangerous. Aggressive cancers, on the other hand, demand urgent action. And sometimes a cancer that starts off as a "pussycat" will later turn into a "tiger".



Sarcosine, an amino acid, offers the possibility of spotting when a cancer becomes aggressive with a straightforward urine test.



Scientists identified the molecule after screening 1,126 break-down chemicals or "metabolites" in healthy prostate tissue, localised prostate cancer, and metastatic or spreading tumours.



They found 60 metabolites that were present in tumour cells but not benign tissue. Of these, about 10 molecules had levels which increased dramatically during cancer progression.



Sarcosine was picked from the 10 as the most promising marker because its levels were raised in localised disease and dramatically increased in spreading cancer.



Laboratory experiments showed that the molecule actually played a role in driving the disease. Manipulating benign cells so they produced sarcosine caused them to become cancerous and invasive. Conversely, shutting down sarcosine production held back the growth of cancer cells.



The findings are reported in the latest issue of the journal Nature.



Senior study author Dr Arul Chinnaiyan, director of the Michigan Center for Translational Pathology at the University of Michigan in Ann Arbor, US, said: "One of the biggest challenges we face in prostate cancer is determining if the cancer is aggressive.



"We end up over treating our patients because physicians don't know which tumours will be slow-growing. With this research, we have identified a potential marker for the aggressive tumours.



"When we're looking at metabolites, we're looking several steps beyond genes and proteins. It allows us to look very deeply at some of the functions of the cells and the biochemistry that occurs during cancer development."



Levels of sarcosine were found to be elevated in 79% of the metastatic prostate cancer samples analysed and 42% of the earlier stage cancer samples.



The tests showed that the amino acid was a better indicator of advancing disease than prostate specific antigen (PSA), the blood biomarker currently relied upon to monitor prostate cancer.



Dr Chinnaiyan said more work was needed to establish whether drugs that target sarcosine might be useful treatments.



The scientists now plan to take a closer look at the other nine potential biomarkers. Ideally, a test for diagnosing aggressive disease would not rely on just one metabolite.



John Neate, chief executive of The Prostate Cancer Charity, said: "Multiple and complex processes occur inside prostate cells to make prostate cancer develop and spread outside of the gland, which it may do in some men. Many scientists focus their work on deciphering the pathways, messages and processes that make these changes happen. If the researchers find markers that only appear when cancers are aggressive or spreading they would have identified one aspect that could be useful as a test, or a target for intervention by a drug. In this early new research the scientists have done exactly that.



"It is too soon to say if the results of this study are a blind alley or a breakthrough, but so far results are promising enough for research to continue and could lead to the development of a new test for prostate cancer. Men need progress in this kind of research, especially into the prostate cancers that can kill."

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