Pointing the way in treatment of prostate cancer

An Irish scientist has found markers that can give an early warning of the presence of cancer in the prostate gland, writes DICK…

An Irish scientist has found markers that can give an early warning of the presence of cancer in the prostate gland, writes DICK AHLSTROM

CHANGE IS USUALLY a good thing unless it is occurring within our genetic blueprint. Unwanted changes in how our DNA works can lead to disease, particularly cancers.

Yet change of this kind is also providing new ways to detect cancer and points towards new approaches for treating it. The work is based on epigenetics, the study of changes in how DNA functions.

Irish Cancer Society research fellow Dr Antoinette Perry is deeply involved in this work. She was lead author in a review of epigenetics published last month in the journal Nature Reviews Urology.

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The review article argues that the epigenome could become a therapeutic target in the diagnosis and treatment of prostate cancer.

New approaches in this area would be very welcome given prostate cancer is the second most common form of the disease here after skin cancer. One in 12 men will develop prostate cancer over their lifetime, according to figures from the Irish Cancer Society.

Perry is based at the Institute of Molecular Medicine at St James’s Hospital and completed her PhD as part of the Prostate Cancer Research Consortium. “My area of research looks at epigenetic changes that occur in the early stages of prostate cancer,” she explains.

Our DNA controls the biochemistry inside our cells, providing the instructions to make the various substances our cells need to function.

Scientists have long studied unwanted changes to our DNA, mutations that can lead to cancer. Epigenetics is a bit different however, it does not look at changes in the DNA itself, it is the study of changes in how the DNA works.

The functioning parts of DNA, our genes, work in concert like an orchestra. There is an interplay between the genes, when they switch on and off and how they react to these changes, with the patterns inherited just like our DNA.

“Epigenetic changes are changes that occur in the DNA without altering the DNA code,” Parry explains. “It switches the gene on and off. When you think about cancer, it is a disease where lots of different changes happen. Epigenetic changes are another route to cancer development.”

Epigenetics emerged as a field of study in the mid-1980s and has become very important, she says. “We can use it as a tool to detect cancer cells in the patient. We are looking for markers.”

She and colleagues are focusing on one of the changes, a chemical alteration called DNA methylation. If this happens in the wrong way it can cause problems.

“Important genes that have a regulatory effect in the cell get switched off and this contributes to the development of cancer,” Perry says. “There is a loss of the methylation balance in cancer.”

Yet this also represents an opportunity. “Methylation changes occur early in the step-wise progression of cancer,” she says, so methylation patterns can provide a very early warning of prostate cancer.

They also point towards the type of cancer involved. Different genes get methylated in the various forms of prostate cancer, so the researchers can also see whether it is the more aggressive form of the disease.

“One of the big problems is being able to detect the big ones, the cancers likely to metastasise [spread],” she says.

Aside from its predictive power, the approach may also lead to new therapies. The goal would be to attempt to reverse the inappropriate methylation and so switch the tumour suppressor genes back on. This could be done using demethylating agents, she suggests in her Nature review.

This could offer new treatments for patients with advanced disease or those with the more aggressive forms.