Mice have been shortening life spans for centuries by surprising us in places they're not supposed to be — nearly sending us into cardiac arrest along the way.
But some mice on Mayo Clinic's Arizona campus are surprising in a different way, helping researchers unlock new and improved treatments for multiple myeloma, the second most common blood cancer in the United States. "We've made a lot of progress in recent years. But even now, myeloma usually recurs after treatment. We're still looking for new and better therapies," Leif Bergsagel, M.D., a cancer genetics researcher, tells Mayo Clinic's Research Magazine, Discovery's Edge.
And that is where our friend the mouse comes in. "Our model is faithful to what actually happens in the development of tumors in human disease," biochemist and molecular biologist Marta Chesi, Ph.D., tells Discovery's Edge. "We can now rapidly screen compounds in our mouse to prioritize which drugs should enter clinical trials."
So how did Drs. Chesi, Bergsagel, et al. come to achieve all of this? By "hijacking" multiple myeloma's "cellular machinery," of course. And, Discovery's Edge reports, by creating "a transgenic model" that allows researchers to "capture complexities in the interaction of cancer and the immune system" that other lab models cannot. They "replicate the process of tumor-cell evolution observed in humans, and the crosstalk between tumor and the immune system," Dr. Chesi tells the publication.
Drs. Chesi and Bergsagel arrived at this scientific "breakthrough" by focusing their attention on a specific gene called MYC, the "activation" of which "turns out to be critical to the development of multiple myeloma," according to the magazine. But by "exploiting a natural process" called "somatic hypermutation that occurs in immune cells when they mobilize against a foreign molecule, such as cancer," Drs. Chesi and Bergsagel were able to essentially activate this gene at will in their mouse model.
And by doing so, the magazine reports the researchers gave themselves a much more accurate predictor of which multiple myeloma treatments are likely to work in both mice and humans. "We can now say there is a 90 percent chance that a drug that doesn't work in the model will be inactive in humans," Dr. Chesi says. "On the other hand, if a drug works well to eradicate tumor in the mice, there is a 70 percent chance the drug will also work in human patients."
And that, Dr. Bergsagel says, can go a long way toward weeding out which cancer drugs should, and should not, go to clinical trial. "It's almost unheard-of in cancer to have a model that is this predictive," he tells the publication.
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