Hopkins researchers develop method to predict response to chemotherapy

Researchers at the Johns Hopkins Oncology Center uncovered a genetic alteration that appears to predict how individuals with an aggressive type of brain cancer will respond to chemotherapy.

The discovery, published in the November 9, 2000, issue of the New England Journal of Medicine, emerged from analysis of tumor samples from 47 patients with glioma, all of whom received standard treatment with the drug, carmustine. In 19 of the patients, the methyl-guanine-DNA methyltransferase (MGMT) gene appeared in a chemically altered form and 12 of these 19 had significantly better responses to chemotherapy, including regression of the tumor and increased long-term survival. This is compared with one patient of 28 with unaltered MGMT genes who responded to the chemotherapy. Patients with altered MGMT genes lived an average of 13 months longer than the other patients.

The MGMT gene is altered through a biochemical process known as methylation. The Hopkins scientists speculate that the normal, so-called unmethylated MGMT genes support repair of DNA damage, including damage caused by chemotherapy drugs, and therefore inhibits effectiveness of the drug. When the gene is altered or methylated, however, repair activity is blocked, allowing the anticancer drugs to attack the cancer cells unchecked.

The researchers currently are investigating agents that will block the MGMT gene and increase tumor sensitivity to carmustine. "The ability to detect the methylated form of the MGMT gene may provide a new way of pre-selecting some cancer therapy based on a tumor's chemical profile," says James G. Herman, M.D., assistant professor of oncology at Johns Hopkins and principal investigator of the study.

"The most exciting aspect of this research is that we can begin applying it to therapy right away," says Manel Esteller, M.D., Ph.D., research fellow at the Oncology Center and first author of the paper. "We don't have to wait for new drugs to be develo

Contact: Vanessa Wasta
Johns Hopkins Medical Institutions

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