Dr Bostjan Humar and Assocaite Professor Parry Guilford
In 1998 researchers from the University's Cancer Genetics Laboratory (CGL) led the world in discovering the genetic defect that predisposes towards the disease known as hereditary diffuse gastric cancer.
The team, led by Associate Professor Parry Guilford and Dr Bostjan Humar, has now unravelled the complicated mechanisms behind the cancer's earliest stages of development, providing potential targets for early treatment with new-generation drugs and giving hope that the disease can be stopped early without the need to remove the stomachs of affected or vulnerable people.
This disease affects families around the world, but its grimmest toll has fallen on one large Mäori whanau in particular.
A research partnership was established between CGL and the whanau, and molecular genetics techniques were used to study stomach tissue samples removed from whanau members as part of a preventive surveillance programme.
"We were able to track the cancer's beginnings in a specific part of the stomach, how it then changes to form tiny tumours and, finally, how it is able to invade other parts of the body," Humar says.
As a result the researchers have established a detailed model of the cancer's development, which had been largely a mystery. They have also discovered that the mechanisms behind its initiation are vulnerable to new types of drug therapy.
"We found that the vital mechanism leading to the invasive state involves activating a specific type of protein," says Humar. "Drugs which inhibit this protein are being evaluated for safety and, if given the go-ahead, could be used to slow the disease."
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 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, 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.
FUNDING
Health Research Council