Improved rationale for attacking colorectal cancer

Some people respond very well to chemotherapy or radiotherapy for colorectal cancer, while others hardly respond at all – a fact that has been a bit of a mystery until now. A team of Garvan scientists believes the outcome may depend on a gene called ‘MCC’ – which happens to be expressed at low levels in a subset of colorectal cancers. Their findings give them a rationale for checking patients' responses to therapy.
Improved rationale for attacking colorectal cancer

Dr Maija Kohonen-Corish and Dr Laurent Pangon

Media Release: 17 January 2011

Some people respond very well to chemotherapy or radiotherapy for colorectal cancer, while others hardly respond at all – a fact that has been a bit of a mystery until now.

A team of Australian scientists believes the outcome may depend on a gene called ‘MCC’ – which happens to be expressed at low levels in a subset of colorectal cancers.

Ironically, lack of MCC in tumours probably helps those cancers to grow, as well as helping aggressive therapies to kill them.

Drs Laurent Pangon and Maija Kohonen-Corish, who have been investigating the tumour cells of over 200 colorectal cancer patients, say their new insight into the function of MCC now gives them a rationale for checking how each person responded to therapy. Their findings are published in Genes and Cancer, now online.

“We’ve shown that MCC has an important role to play in a well-known phenomenon known as the ‘DNA damage response’,” said Dr Pangon.

“Every cell in the body is regularly exposed to DNA damage from things like toxins, viruses or radiation.”

“Any genes that help regulate this DNA damage – find it, correct it, or make sure cells deal with it – are really important. If such genes lose their effect, DNA damage would accumulate, and cancer would probably develop.”

“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.”

“If you lose MCC, therefore, you lose the ability of the cell to repair DNA damage.”

“We know that 50% of our patient cohort had tumours with a defective MCC gene, which causes lack of expression. We believe that these patients are more responsive to radiotherapy or some types of chemotherapy.”

“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.”

The group has developed a biomarker test that can identify MCC defects in tissue. Pangon says that the next step is to do a retrospective study of the patient cohort, checking therapy response against the presence of the biomarker in each patient.

“I think 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. Some patients do really well, and others don’t respond at all,” he said.

“Our study has the potential to provide a scientific explanation as to why some patients respond to treatment better than others and a practical test to identify those patients who are likely to respond.”

ACKNOWLEDGEMENTS

This research was supported by the Cancer Council NSW, the Cancer Institute NSW and the Clive and Vera Ramaciotti Foundations.

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