Melbourne researchers believe they have found what causes the onset and acceleration of bowel cancer, opening up the possibility of new ways to treat the disease.
Bowel cancer is the third most common cancer in Australia and claimed nearly 4,000 lives in 2012, while 15,840 people were newly-diagnosed.
Around 80 people die each week from the disease.
Now researchers from Melbourne’s Peter MacCallum Cancer Centre have found a failure in a two-part protective “braking system” in the bowel cancer cells, which caused the acceleration of disease and the development of resistance to cancer treatments.
They said the discovery showed for the first time how an orderly process of orchestrated cell division failed in two ways, triggering what is known as chromosomal instability.
Lead author Professor Rob Ramsay said the result of chromosomal instability in bowel cancer had been known for some time, but they did not know what caused it.
“Previously, in most bowel cancers, we thought this instability built up randomly over time as cancer cells evolved, while a signalling network, call the Wnt pathway, held cells back from chromosome chaos,” he said.
“Now we have proven this instability begins immediately with the breakdown of the Wnt pathway, which occurs in two steps and sets off an unstoppable acceleration of disease.
“Just as the loss of firstly the handbrake, followed by the secondary loss of a foot brake, both combine to allow a car to career down a hill.”
Chromosomal instability was found in 85 per cent of tumours in people with bowel cancer.
Professor Ramsay says the “double breakdown” in the Wnt pathway sparked complex evolution in the genetic make-up of bowel cancers.
“We analysed cells taken from human patients during bowel cancer surgery, and compared them to cells observed in the pristine, primary environment of a test tube and in mouse models, and we observed the same changes in cells and the same extraordinary effects,” he said.
“In only a few days, the transition from healthy to cancerous cells is visibly stark.
“The dramatic genomic changes cells go through gives the cancer a breadth of opportunities to rapidly evolve, to deceive and outflank the cancer treatments.”
Professor Ramsay said the findings open up potential new treatment possibilities.
“This fundamental new information reaffirms why the Wnt pathway should be a high priority target of new treatment development, and the genetic clues uncovered by our research will help guide the selection of patients for different therapies, some of which are currently available,” he said.