Research offers hope to Maori family with rare cancer

ODT 20.3.2007

Ground-breaking University of Otago research has brought new hope that a rare, deadly hereditary cancer can be stopped without removing the stomachs of its victims.
It has also opened the door to treat the globally significant, non-genetic form of the disease, and the chance to test a theory that cancer grows from a detectable — and potentially beatable — stem cell.

The Cancer Genetics Laboratory yesterday confirmed it had unlocked the genetic mechanisms behind the earliest stages of diffuse stomach cancer. The once-mysterious cancer has been found in 70 families worldwide, but the breakthrough came from a decade-old surveillance and treatment programme with a Maori family in the Bay of Plenty. The collaborative project in 1998 found a genetic defect predisposed the family to the disease.

Project co-leader Dr Bostjan Humar said molecular genetics ultimately helped the team discover that the mechanisms that kick-started the cancer might be vulnerable to new drugs.

Some of these drugs were coincidentally already being tested in clinical safety trials.
Protein inhibitors that could slow or stop the cancer becoming invasive were also being tested, Dr Humar said.

The study revealed hundreds of microscopic tumours in the stomachs, which were otherwise undetectable when they were in the body, Dr Humar said.
The team used the stomach samples to see how the cancers developed. Researchers watched the disease “while it was still parked in the garage”, he said.
They established a model to track the cancer’s beginnings in the stomach, how it changed to form tumours, and how it invaded other parts of the body.
Associate Prof Parry Guilford said the research had also been extended to the non-hereditary form of the disease, one of the more frequent fatal cancers worldwide. About 900,000 people were diagnosed with the cancer each year.
The laboratory was also researching whether this cancer started from a so-called “cancer stem cell” — something the research model suggested was “a strong possibility”.

If those cells, which account for less than 1% of a tumour, could be isolated and controlled, they could revolutionise cancer therapy, Prof Guilford said.
A single cancer stem cell is thought to be enough to regenerate a tumour. Some appear to resist current therapies and might be responsible for relapses, Prof Guilford said.

Prof Guilford said 50 of the 140 people in the McLeod family from the Bay of Plenty had the genetic mutation that gave them a 70% risk of developing the cancer.
Nineteen of them had early stomach cancer. They had had gastrectomies, and were likely to be cured. Another family member, who was diagnosed with the advanced disease, had died. Ninety others in the family do not carry the mutation.

The findings are published in the international journal Cancer Research.