Brief Oncogene Inhibition Prevents Tumor Development

Using a transgenic mouse model, investigators have shown that brief drug-induced inactivation of the MYC gene prevented transplanted cancer cells from developing into mature tumors, and subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. This study was published in the July 5, 2002, issue of Science.

"Nobody had ever seen that turning off a cancer gene for a few days caused irreversible change,” said Dr. Dean Felsher, assistant professor of oncology at the Stanford University Medical Center (Palo Alto, CA, USA; www.stanford.edu) and lead researcher. "Most people thought that cancer would come back, once treatment that turned off an oncogene stopped.”

Researchers developed a line of bone cancer cells containing an altered version of MYC that could be shut down by adding a molecular switch. Mice injected with these cells went on to develop bone cancer. When the mice were treated to inhibit MYC, the cancer cells reverted to normal bone cells. After 10 days, treatment was stopped, allowing the gene to resume protein production. Instead of restarting cancerous growth, the transplanted cancer cells died.

Mice with MYC gene switched off for 10 days survived four times longer than untreated mice with bone cancer. The cancer reappeared in some of the treated mice, but went back into remission with another round of temporary MYC-disabling treatment. In many types of cancers, the MYC gene produces excess protein that allows the rapid growth that is characteristic of cancer cells. Thus, the new finding should apply to a lot of tumors.

"You do not always need to shut the oncogene off permanently,” Dr. Felsher said. "That could change the way you think about treating cancer.”



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