WASHINGTON, D.C.—By the time many people find out they have cancer, the disease has spread and can't be cured. But researchers may have found a new chink in the armor of breast cancer: a short stretch of RNA that can curb the growth of metastasized breast tumors in mice long after the cancers start growing. The finding, which could point to new cancer drugs, was one of several possible payoffs from so-called microRNAs highlighted here this week at the annual meeting of the American Association for Cancer Research (AACR).
MicroRNAs (miRNAs) are short stretches of RNA that control the expression of genes and have been linked to many diseases, including cancer. Graduate student Scott Valastyan and others in cancer biologist Robert Weinberg's lab at the Massachusetts Institute of Technology (MIT) in Cambridge, Massachusetts, found that a miRNA known as miR-31 is present at unusually low levels in breast cancer tumors that eventually metastasized compared with normal breast cells (MiR-31's normal function in the body is unclear). Last summer, the MIT team reported that when it ramped up miR-31 levels in breast cancer cells implanted into cancer-prone mice, primary tumors kept growing but metastatic tumors decreased.
In their latest work, Valastyan and others have been studying what happens if they turn on miR-31 at various times after metastasis has begun. They boosted the production of miR-31 in breast cancer cells using a genetic switch that turns the miRNA on only when the mice are fed the antibiotic doxycycline. Then they implanted the cancer cells into the mammary pads of mice or injected the cells into the animals' tail veins and monitored the growth of metastatic tumors in the animals' lungs over the next 3 months.
Even if the researchers waited as long as 8 to 11 weeks to turn on the miR-31, the animals had up to 60% to 80% fewer metastases than did control mice. The miR-31 appears to both inhibit metastatic growth and shrink metastases, Valastyan says.
Although other miRNAs can promote or suppress metastasis, miR-31 may be the first that has effects on advanced metastatic tumors, says cancer immunologist Charles Drake of Johns Hopkins University in Baltimore, Maryland, who moderated the late-breaking session where the study was presented. "Clinically, that's very appealing, since many of the patients we treat have had metastatic disease for some time," Drake says. The challenge will be finding ways to activate miR-31; so far, nobody has found a drug or other safe way to switch on an miRNA in humans.
The talk was one of many miRNA studies presented at the AACR meeting. In another presentation, for example, Sumaiyah Rehman, a graduate student in the lab of Dihua Yu at M.D. Anderson Cancer Center in Houston, Texas, reported that miRNA-21 turns off a gene called PTEN that makes breast cancer cells resistant to Herceptin, a widely used drug. Measuring tumor miRNA-21 levels could help identify women who won't respond to Herceptin and should be spared its toxicity, she said. And a team at New York University (NYU) School of Medicine has found a set of miRNAs that appear to help melanoma cells get through the blood-brain barrier and metastasize in the brain. The MiRNAs could also be used to spot patients at higher risk for metastasis, according to the NYU researchers.
The overall message, says MIT molecular biologist Phillip Sharp, who moderated a press conference on miRNA: "MicroRNAs are key players in controlling the cellular properties of tumor cells and their study could provide critical insights for future treatment of cancer."
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