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Colorectal cancer mystery solved

Australian research has identified a defective gene which explains why some colorectal cancer patients respond very well to radiotherapy but others not at all.

Sydney-based scientists have examined the role played by the gene MCC which, in earlier work, in 2007, they found was awry in around half of all cases of colon and rectal cancer.

The defective gene was a "double-edged sword", said Dr Laurent Pangon, as it appeared to both encourage a tumour to develop but also make these less resistant and easier to kill off with radiotherapy.

"Our findings show that MCC appears to be involved at a kind of DNA damage checkpoint, when the cell recognises that there is DNA damage and that it needs to do something to correct it," Pangon .

"If you lose MCC therefore you lose the ability of the cell to repair DNA damage ... and cancer would probably develop."

Pangon, working along with Dr Maija Kohonen-Corish also from the Garvan Institute for Medical Research, studied how 200 colorectal cancer patients responded to their treatment.

While surgical removal is the primary way to combat these cancers, patients can also undergo anti-cancer therapies to kill off any cancer cells left behind or tumours which surgeons could not reach.

Pangon said those patients with a defective MCC gene were found to have a much improved response to radiotherapy, and some types of chemotherapy, as their tumours were much less resistant to treatment.

"That is because those therapies kill cancer cells through inducing DNA damage and if the DNA damage response of the tumour is already defective, the therapies work better," he said.

"Our study has the potential to provide a scientific explanation as to why some patients respond to treatment better than others."

The researchers also developed a test which can identify those colorectal cancer patients who have the defective gene, and so those who do not and were best diverted to alternative therapies.

It is part of the new frontier in cancer treatment, in which a patient's genetic make-up can point doctors to the anti-cancer treatment most likely to work.

The research is published online by the journal Genes and Cancer.

"This study is important for colon cancer but even more important for rectal cancer, because rectal cancer has a real disparity when it comes to radiotherapy which is not well explained," Pangon said.

"Some patients do really well, and others don't respond at all."


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