Gene Mutation Linked to Chemo-Resistant Colon Cancer

WEDNESDAY Jan. 4, 2012 -- Some people with advanced colorectal cancer are resistant to some types of chemotherapy, and a mutation in the so-called TFAP2E gene may play a part in that resistance, German researchers report.

Knowing which patients carry the mutation might help doctors tailor treatments or develop new targets for therapy, the researchers said.

"In our study, we identified a gene which is frequently altered in colorectal cancer," said lead researcher Dr. Matthias P.A. Ebert, an assistant professor of internal medicine at the University of Magdeburg. "This genetic alteration is associated with increased resistance to chemotherapy and radiation in colorectal cancers."

The findings appear in the Jan. 5 issue of the New England Journal of Medicine.

For the study, Ebert's team analyzed how the TFAP2E gene functioned in colorectal cancer tumors.

Overall, they looked at more than 200 patients undergoing chemotherapy for advanced colorectal cancer. Among the first group of 74 patients, 38 had a mutation in this gene, the researchers found.

Mutated tumor cells in these and other patients made the cells resistant to fluorouracil, a widely used type of chemotherapy. However, the mutation did not make the tumor resistant to irinotecan or oxaliplatin, two other chemotherapy drugs, the researchers found.

In the rest of the patients after the first group, the researchers found a similar association between the TFAP2E gene mutation and tumors not responding to chemotherapy with fluorouracil.

"Chemotherapy and radiation is very helpful in the majority of patients with colon cancer and rectal cancers, respectively," Ebert said.

"If our studies are confirmed in prospective trials and by other groups, alteration of the TFAP2E gene could help identify subgroups of patients with colorectal cancer that would show good response to chemotherapy or radiation," he said.

Dr. Durado Brooks, director of the prostate and colorectal cancer division at the American Cancer Society, said "this is one more brick in the wall that is slowly helping us build our knowledge and understanding of how to attack cancer in new and different ways."

"If the findings are corroborated by other investigators, it could lead to testing of tumors to find if those tumors are likely to be resistant to fluorouracil-based chemotherapy," Brooks said.

It could also help identify new targets for treatment, he said.

Brooks thinks other gene mutations also affect how well chemotherapy works. Some genetic testing is done now for this purpose, he said; however, it's too soon to tell whether TFAP2E may be added to those tested, he said.

"This is a long way from moving into clinical practice," Brooks said.

"We need to know a lot more of how this impacts actual patients; all this data is based on looking at things under a microscope as opposed to investigating the impact of treatment in patients, which may turn out to be a little different," he said. "It's not ready to move from the lab bench to the bedside yet."

More information

To learn about colon cancer, visit the American Cancer Society.

Posted: January 2012


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