Australian researchers have identified some of the earliest causes of bowel cancer, revealing how the disease begins, grows and develops resistance to drug treatments.
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The breakthrough could lead to better use of current chemotherapy drugs and to the development of new treatments for the disease - the third-most-common cancer diagnosed in Australia.
Rob Ramsay, lead researcher and head of the cancer cell biology program at Peter MacCallum Cancer Centre, said the discovery related to 85 per cent of tumours found in people with bowel cancer who did not tend to have a family history of the illness.
His team had identified how a two-part protective "braking system" in the body failed in these cells, causing the onset and acceleration of the disease, Professor Ramsay said.
While the chromosomes inside bowel cancer cells had long been known to show instability, making their behaviour difficult to predict or target, scientists did not know how this instability began, he said.
After taking cells from about 600 patients and comparing them to cells in test tubes and mouse models, the scientists could see the breakdown of the two-step protective braking system unfolding and triggering the chromosomal chaos.
"In only a few days, the transition from healthy to cancerous cells is visibly stark and the dramatic genomic changes cells go through gives the cancer a breadth of opportunities to rapidly evolve and to deceive and outflank the cancer treatments eventually employed to fight it," Professor Ramsay said.
Until now, scientists thought the chromosomal instability built up randomly over time as cancer cells evolved, while a signalling network called the Wnt pathway held cells back from chromosome chaos. This study shows the instability begins immediately with the breakdown of the Wnt pathway, which occurs in two steps, setting off the disease.
The finding, the culmination of five years' work, had already prompted discussion about whether two commonly used chemotherapy drugs could be used differently to improve their efficacy.
"We think some of the drugs that are more useful in this process might be employed earlier," he said.
It also opened new avenues for scientists trying to develop new treatments for bowel cancer, he said.
The research, conducted by Dr Huiling Xu and 13 other scientists from universities, was published in the journal Cell Reports.
In 2012, nearly 16,000 Australians were diagnosed with bowel cancer and almost 4000 died from it.
