18 Nov 2013

One of our leading researchers has discovered a protein that can help distinguish between prostate cancers that are life-threatening and those which are much less aggressive.

Dr Hayley Whitaker, based at Cambridge Research Institute, has carried out a study, part-funded by Prostate Cancer UK, which has found that there are much higher levels of the protein, NAALADL2 in prostate cancer tissue compared with healthy tissue - and that the protein is also associated with the aggressiveness of the disease.

At the moment, diagnostic tests for prostate cancer can’t reliably tell us if cancer is aggressive and needs treating straight away or is slow-growing and won’t need any treatment. This means that some men diagnosed with prostate cancer are faced with an almost impossible decision: to have treatment and risk long-term, potentially debilitating side effects when the tumour might be relatively benign. Or, to have their cancer monitored and run the risk that the tumour might spread.

Dr Whitaker’s research is at an early stage and there’s still a long way to go before we know whether it will translate into a clinically useful test for aggressive prostate cancer. However, this research takes us a step closer to our goal where men with aggressive tumours can have immediate treatment, and men with low-risk tumours can have the confidence avoid or delay treatment.

Dr Iain Frame, Director of Research at Prostate Cancer UK said:

“The results of this study are encouraging but we still have a long way to go. 

Being able to distinguish aggressive from non-aggressive prostate cancers could transform the outlook for the 40,000 men who are faced with a diagnosis of the disease every year. The current diagnostic process is at best inadequate. All too often men are faced with the difficult decision of whether to endure life-changing side effects from treatment for cancers which may never cause them any harm. Others however, are left with more aggressive cancers that are untreated until it’s too late. If we are to save more of the 10,000 men who lose their lives to this disease every year this urgently needs to be addressed.

The challenge is now to see if this research can be translated into real benefits for men diagnosed with the disease. We will watch with great interest for developments in this area.”

Under the microscope

The researchers conducting this study knew they were onto something exciting when they observed higher levels of the protein NAALADL2 in cancerous than non-cancerous prostate samples.

Even more excitingly, they found that the expression levels of this protein (how much there is of it) was also linked to how aggressive the prostate cancer was – meaning that aggressive prostate cancer samples had higher levels of NAALADL2 than less aggressive samples. 

In addition to this, the researchers found that overall, patients with high levels of NAALADL2 had worse outcomes after prostate cancer surgery than those with lower levels. 

These results are really promising, and suggest that NAALADL2 might be a useful diagnostic marker for aggressive prostate cancer – something we don’t have at the moment.  However, in order to turn exciting laboratory discoveries into practical tools, like diagnostic tests, it’s important to know what the protein in question does and how it works.

So to start to answer these questions, the researchers looked in prostate cancer cells and found that NAALADL2 increased cell movement and movement into other cells, suggesting that it might help the cancer to spread.

The researchers also found out that NAALADL2 was often expressed at the same time as nine other genes, many of which are regulated by androgens – steroid hormones known to promote prostate cancer growth – and have previously been linked to cancer development.

At the end of these experiments, the researchers concluded that changes in levels of NAALADL2 can impact cell signaling pathways that promote cancer growth – meaning that this protein might one day be useful in a test to diagnose prostate cancer, and to tell the difference between aggressive and non-aggressive disease.

The results from this high quality study are very promising and hugely exciting, but it’s also really important to remember that the story isn’t finished yet. This research is at a very early stage and there’s still a long way to go before we know whether this exciting research will translate into a clinically useful test for aggressive prostate cancer.

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