Cancer usually results after a cell accumulates a handful of mutations in cancer-related genes called oncogenes or tumor-suppressor genes. Researchers had thought that cancer cells would side-step attempts to fix any single genetic change, especially after treatment ends. But in a study published in the July 5 issue of Science, researchers found that by briefly tinkering with only one mutant gene they could forever alter the course of the cancer.
"Nobody had ever seen that turning off a cancer gene for a few days caused irreversible change," said Dean Felsher, MD, PhD, assistant professor of oncology and lead researcher on the study. "Most people thought that cancer would come back once treatment that turned off an oncogene stopped."
Felsher and his colleagues worked with a gene called MYC, which normally tells a cell when to grow or divide. In many types of cancers, such as lymphoma, breast, colon, and prostate, this gene produces excess protein that allows the rapid growth characteristic of cancer cells. "Anything you learn about MYC should be applicable to a lot of tumors," Felsher said. He added that because the gene is so important, any results may carry significant weight.
Felsher created bone cancer cells containing an altered version of MYC that could be shut down by adding a molecular off switch. He then injected those cells into mice, which went on to develop bone cancer. When he fed mice the off switch, MYC production stopped and the cancer cells quickly reverted to normal bone cells. After 10 days, he stopped treatment, allowing the gene to resume churning out protein. Instead of restarting cancerous growth, the cells died.
Mice that had their MYC gene switched off for 10 days survived four times longer than untreated mice with bone cancer. The cancer resurfaced in some of the treated mice, but went back into remission with another round of temporary MYC-disabling treatment. "You don't always need to shut the oncogene off permanently," Felsher said. "That could change the way you think about treating cancer."
Felsher cautioned that his current results may not apply to all cancers. His previous work shows that MYC - like all oncogenes - is a complicated gene that can contribute to cancer by many different mechanisms. Depending on which role the gene is playing in the cell, the effects of shutting it off may vary. "We are trying to understand the genetics of when shutting off MYC will work," Felsher said.
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