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Last Updated: Thursday, 27 December 2007, 08:33 GMT
New genetics fuels cancer hope
By Monise Durrani
Radio 4's The Switching Point

Leukaemia cells
Epigenetics is aiding the fight against leukaemia

It is a whole new science with important implications for the treatment of disease - most notably cancer.

Epigenetics is the study of molecular modifications which sit on top of the DNA in our cells, in effect switching our genes on and off; telling our cells how they should behave.

Scientists are now realising that if those epigenetic markings are disrupted, causing a gene to become incorrectly active or silent, a healthy cell could become diseased.

Research is beginning to uncover the mechanisms behind these switches - and the circumstances under which changes occur.

This opens up a whole new area of therapy which has not been available before
Professor Adrian Bird
Edinburgh University

It is bringing new insight into our biology, particularly the understanding of diseases such as cancer, diabetes, and schizophrenia.

"We can still explain only a small proportion of a person's predisposition to complex disease based on genetics alone," said Vardhman Rakyan, from Queen Mary's School of Medicine in London.

Epigenetics could provide the missing link.

What is really causing excitement is the possibility of new treatments.

"The distinction between epigenetic changes and genetic changes is that epigenetic changes appear to be reversible," said Professor Adrian Bird from Edinburgh University.

"This opens up a whole new area of therapy which has not been available before."

Cancer application

Epigenetics is already making a difference in cancer biology.

A tumour is a lump of cells that grow and proliferate uncontrollably, eventually invading other parts of the body.

There's no question that almost every cancer cell has problems with the epigenetic programming
Professor Moshe Szyf
McGill University

We have hundreds of genes which, when working properly, keep healthy cells in check.

These can be disrupted by damage directly to their DNA - but it's now been realised that epigenetic changes could also be responsible.

"There's no question that almost every cancer cell has problems with the epigenetic programming," said Professor Moshe Szyf, from McGill University in Montreal.

So an increasing focus of research has been to find drugs which can remove these chemical changes.

A common epigenetic change in cancers is DNA methylation - which silences genes.

At the MD Anderson Cancer Center in Houston, Texas, Dr Jean Pierre Issa has been pioneering the use of two epigenetic drug therapies - decitabine and azacitidine.

Rather than killing cancer cells, these drugs remove the aberrant methylation, reactivating genes which had been silenced.

"When I was diagnosed with leukaemia, I was devastated - I thought I was going to die," said 72-year-old Nancy Stanley, a Texas patient who has received this treatment.

Remarkable results

Nancy suffers from Myelodysplastic syndrome (MDS), a bone marrow disorder which disrupts the formation of blood cells.

It's predominantly caused by the methylation of one particular gene, and so has become an ideal candidate disease for epigenetic therapy.

"We have had remarkable results," said Dr Issa.

Epigenetics gives us a whole new way to look at the diagnosis, treatment and assessment of solid tumours
Dr Tim Crook
Breakthrough Breast Cancer

"About half the patients have shown a complete disappearance of all signs and symptoms of disease."

He cautions that this is not an absolute cure; but is optimistic: "In MDS there was no effective treatment two or three years ago - now two of the three drugs currently approved work on this epigenetic mechanism."

The successes in MDS has lead to hopes for other types of cancer.

Understanding epigenetic changes may reveal how tumours develop and become malignant; and could help explain differences in the prognosis of patients.

This in turn will allow doctors to better target cancer treatments.

"We should be very excited," said Dr Tim Crook, of the charity Breakthrough Breast Cancer.

"Epigenetics gives us a whole new way to look at the diagnosis, treatment and assessment of solid tumours."

Massive promise

Dr Crook believes there is huge potential for epigenetics in the early detection of cancer.

He is interested in finding epigenetic markers which could be used for this diagnosis.

Tumours release tiny bits of DNA into the bloodstream - which will be epigenetically altered. So a blood test for abnormally methylated DNA could help doctors catch cancers early in their development.

Crook hopes that in the future, epigenetic screening for common cancers will be part of regular check ups.

"This is where epigenetics will come into its own," he said.

"There is a genuine prospect that will happen in our lifetimes."

Radio 4's The Switching Point is on Thursday 20 & 27 December at 2100GMT. Each episode remains available for 7 days at Radio 4's Listen again page.



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