Prostate cancer research

Research into prostate cancer is focused on finding a test to sort aggressive tumours, known as tigers, from the harmless ones, the pussycats.

"These exciting results will help us to more accurately calculate the risk of developing prostate cancer."

Professor Ros Eeles

Health experts agree that the current examination, the PSA (prostate-specific antigen) test, has major limitations in assessing prostate cancers. In particular, it cannot determine whether a prostate cancer is slow or fast growing.

This means that many thousands of men are being given invasive treatment that they don't need, says Professor Colin Cooper of The Institute of Cancer Research (ICR).

"This is because we've been unable to distinguish them from the men who urgently need life-saving treatment," he says.

Cooper's team at the ICR has been putting its efforts into finding a test that can accurately determine the tigers.

Research has focused on identifying markers that can be used to distinguish harmless from aggressive prostate cancers. Markers are substances that are found in the body when someone has cancer. They are used to help diagnose the disease and determine the best treatment.

"Markers can be used to identify aggressive cancers early so that they may be treated, and to minimise treatment for dormant tumours," says Cooper.

He believes that new tests using markers to distinguish between the tigers and the pussycats could be in use in clinics within "the next couple of years".

E2F3 gene

The team's first breakthrough came in 2004 when they discovered that high levels of the E2F3 gene product were present in aggressive prostate cancer cells. The protein produced by the E2F3 gene is known to have a crucial role in all human cells by controlling their production.

Cooper believes that high levels of the E2F3 protein lead to excessive cell reproduction and the development of a tumour. Tests showed that prostate cancer patients with high levels of the E2F3 protein had more aggressive tumours.

"Research is now under way to translate this finding into a test in the hope that we can identify patients who have aggressive early cancers," says Cooper.

Tissue microarrays

Continuing their research into identifying prostate cancer markers, the team developed the Checkboard Tissue Microarray Method. Many tissue samples, often from different people, are collected together and analysed.

It's a semi-automated process, which means it could be used in the future as a way of screening large numbers of samples for the signs of early prostate cancer.

The technique opened up the possibility for identifying many more markers from tissue samples obtained from a prostate biopsy than was previously possible. "Now we can look at hundreds of markers," says Cooper.

"It will enable us to identify new markers to help us diagnose more accurately patients with aggressive tumours."

2+Edel marker

One of the more significant markers discovered using this technique is 2+Edel, which is present in the more aggressive forms of prostate cancer. This genetic abnormality highlights cancers that are more likely to be fatal.

Markers like 2+Edel will help to identify those patients who require immediate treatment and those who require an 'active surveillance' approach.

Research into identifying markers is pivotal in developing a test for prostate cancer aggressiveness that is far more accurate than the PSA test.

"Prostate cancer markers could save thousands of men undergoing unnecessary surgery and living with debilitating side effects," says Cooper.

Three gene combination test

The 2+Edel marker is actually a duplication of the fusion of two genes, TMPRSS2 and ERG, and much work at the ICR has recently focused on the second of these genes.

In 2010, Professor Cooper's team revealed that particular combinations of three genetic abnormalities, including ERG, significantly impacted on the length of time a prostate cancer patient was likely to survive with the disease.

The study was the first to examine the combined impact of the three abnormalities, all of which have previously been associated with prostate cancer  loss of the PTEN gene and rearrangement of the ERG or ETV1 genes.

Prostate cancer patients with none of the genetic alterations had a good prognosis  85.5% were still alive after 11 years. But the 6% of patients who had lost the PTEN gene, but had neither an ERG nor ETV1 gene rearrangement, had a much higher risk of dying from prostate cancer. Long-term follow-up showed only 13.7% were still alive after 11 years. ICR scientists believe that patients could be tested for these genetic abnormalities to help decide the intensity of treatment they should receive.

Family genes

Research has also looked at how our genetic make-up might determine our risk of developing prostate cancer.

A 2008 study led by Professor Ros Eeles of the ICR found a link between family history and prostate cancer.

The ICR and University of Cambridge scientists found seven genetic variations present in more than half of all prostate cancer cases that each increased a person's risk of getting the disease by up to 60%.

Continuing studies by the same team have now identified a total of 18 genetic variants that increase prostate cancer risk. A man who has all the risk variants would have a one in three lifetime risk of developing prostate cancer.

Scientists have also already found prostate cancer genes that are less common but confer a greater risk. A mutation in the gene BRCA2 increases prostate cancer lifetime risk by up to seven-fold, while a BRCA1 mutation is thought to nearly double risk in men under 65.

There are many different factors that influence the development of prostate cancer, but particular combinations of genes are thought to play a major part.

Eeles says: "These exciting results will help us to more accurately calculate the risk of developing prostate cancer."

Page last reviewed: 30/07/2012

Next review due: 30/07/2014

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