Stomach Cancer Discovery Gives New Hope

Monday 19 March 2007

Stomach Cancer Discovery Gives New Hope to Families

University of Otago genetic researchers have discovered exactly how a deadly hereditary type of stomach cancer develops.

Their findings give hope that the disease can be stopped early without needing to remove the stomachs of affected or vulnerable people.

Researchers from the University’s Cancer Genetics Laboratory (CGL) – which, in 1998, led the world in discovering the genetic defect that predisposes towards the disease – have just published their new findings in the leading international journal, Cancer Research.

The disease, known as hereditary diffuse gastric cancer, affects families around the world, but its grimmest toll has fallen on one large Maori whanau in particular.

Thanks to a research partnership between CGL and the whanau, the complicated mechanisms behind the cancer’s earliest stages of development have been unravelled, providing potential targets for early treatment with new-generation drugs.

The research team, led by Associate Professor Parry Guilford and Dr Bostjan Humar, used molecular genetics techniques to study tissue samples of stomachs removed from whanau members. They were taken out as part of a preventive surveillance programme set up for the whanau.

Study of the removed stomachs revealed hundreds of microscopic tumours which were undetectable while they were still in the body.

Dr Humar says that by using samples from stomachs affected by the cancer, the team could closely examine how the tiny cancers developed before they progressed towards their deadly conclusion.

“We were able to look at the disease while it was still parked in the garage, so to speak.”

The researchers have now established a detailed model of the cancer’s development, which had been largely a mystery, Dr Humar says.

“We were able to track its beginnings in a specific part of the stomach, how it then changes to form the tiny tumours and, finally, how it is able to invade other parts of the body.”

They discovered that the mechanisms behind its initiation are vulnerable to new types of drug therapy.

“The kinds of drugs that would interfere with this early step already exist and are currently in clinical safety trials.

“Also, we found that the vital mechanism leading to the invasive state involves activating a specific type of protein. Drugs which inhibit this protein are being evaluated for safety and, if given the go-ahead, could be used to stop or slow the disease.”

Associate Professor Guilford says their findings have also been extended to the non-hereditary form of the disease, which is the second most frequent cancer worldwide, with 900,000 new cases each year.

The CGL, which is part of the newly-formed Centre for Translational Cancer Research, is now pursuing research into whether this cancer originates from a so-called “cancer stem cell” – a strong possibility pointed to by their model.

The concept of these stem cells, which account for less than one per cent of a tumour, is expected to revolutionise cancer therapy, Associate Professor Guilford says.

“A single cancer stem cell is thought to be enough to regenerate a tumour. They appear resistant to current therapies and it is believed that they are likely to be responsible for the high relapse rates of most cancers,” he says.

The current study was funded by the New Zealand Health Research Council.

ENDS

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