Cancers Resistant to Chemotherapy Because of "Notch Signalling"


Scientists at the Harry Perkins Institute of Medical Research have made an exciting discovery which may lead to more effective chemotherapy treatments of bowel cancer patients.

A paper, which has just been published by Britain's highest cancer journal, examined bowel tumour tissues from 441 consenting patients undergoing surgery and chemotherapy to treat their cancers at Sir Charles Gairdner Hospital in Nedlands.

The researchers found that genes involved in a process called "Notch signalling" caused tumours to grow quickly when switched on by the bowel cancers, leading to a lower survival rate for patients.

"Normally Notch signalling in the colon is at low levels in healthy adults, but it's been shown through studies on colon cancer cell-lines that when tumours learn how to switch it on, they become much more resistant to chemotherapy," explained Perkins Researcher, Dr Patrick Candy.

"The Perkins team looked for the first time at Notch signalling in human colon cancer patients and we saw a very dramatic result," he said. "For example, one protein we studied (SOX9) showed patients had an 8-fold higher risk of death when it was found at high levels."

"Our work is leading to the point where medical professionals may be able to test levels of these Notch proteins and use it to decide whether Notch inhibitory drugs might be helpful in making chemotherapy treatment work better."

Dr Candy says that although the study has come up with a statistically powerful result, significantly more work is needed before 'Notch testing' could enter into clinical practice in pathology.

The authors of this paper are from the Laboratory for Cancer Medicine, led by Perkins Director, Professor Peter Leedman. Their study, Notch induced transcription factors are predictive of survival and 5-flououracil response in colorectal cancer patients has been published by the British Journal of Cancer.

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