03:28pm Friday 22 September 2017

Improved rationale for attacking colorectal cancer

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 a Cancer Council NSW Grant.

 

ABOUT GARVAN

The Garvan Institute of Medical Research was founded in 1963.  Initially a research department of St Vincent’s Hospital in Sydney, it is now one of Australia’s largest medical research institutions with over 500 scientists, students and support staff. Garvan’s main research programs are: Cancer, Diabetes & Obesity, Immunology and Inflammation, Osteoporosis and Bone Biology, and Neuroscience. The Garvan’s mission is to make significant contributions to medical science that will change the directions of science and medicine and have major impacts on human health. The outcome of Garvan’s discoveries is the development of better methods of diagnosis, treatment, and ultimately, prevention of disease.

 

All media enquiries should be directed to:

Alison Heather
Science Communications Manager

M: + 61 434 071 326
P: +61 2 9295 8128
E: a.heather “a” garvan.org.au

 


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