Cancer immunotherapy can lead to inflammation of the heart muscle
The research required a marriage of scientific disciplines and areas of expertise, notes co-senior author Goutham Narla, M.D., Ph.D., chief of the division of genetic medicine in the department of internal medicine at the U-M Medical School.
"It's an illustration of how collaboration and team science can solve some of the questions like this that scientists have been asking for many years," Narla says. "Solving the structure without the biological knowledge of how best to apply it against cancer, would only be half of the story. And if we were just activating PP2A, killing cancer cells and slowing the growth of cancer without the structural data -- that would be a really nice half-story as well. But working together, we now have a story about being able to drug this previously undruggable tumor suppressor."
The study was led by first authors Daniel Leonard, an M.D. and Ph.D. student and member of Narla's lab when the research was at Case Western Reserve and the Case Comprehensive Cancer Center, and research scientist Wei Huang, Ph.D., of the Taylor lab.
There has been a lot of activity and excitement in recent years around the development of kinase inhibitors -- small molecule compounds that go after the protein kinases whose dysfunction is involved in the explosive growth and proliferation of cancer cells. That is, turning off cancer's "on switch," Leonard explains.
The new research attacks cancer from the opposite side of the equation, turning on cancer's "off switch" by stabilizing protein phosphatases whose malfunction removes a key brake on cancer growth.
In the paper, the researchers speculate how a combination of both approaches simultaneously might offer an even more powerful one-two punch -- potentially helping to overcome cancer's ability to evolve to thwart a singular approach.
The binding pocket we identified provides a launch pad for optimizing the next generation of SMAPs toward use in the clinic -- in cancer, and potentially other diseases." Wei Huang, Case Western Reserve University Source:
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