Once leiomyosarcoma, now muscle | Cold Spring Harbor Laboratory

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“Every successful drug has its origin story. Research like this is the soil from which new drugs are born,” says Christopher Vacock, a professor at the Cold Spring Harbor Laboratory.

Illustration of RMS cells transforming into muscle cells
The animation model above shows the transformation of RMS cells into healthy muscle cells. When NF-Y is depleted from the cells, the cancer stops multiplying and begins to acquire typical muscle features and functions. The micrographs in the bottom row capture real cells before and after this transformation.

For six years, Vacock’s lab has been on a mission to turn sarcoma cells into regularly functioning tissue cells. Sarcomas are cancers that form in connective tissues such as muscle. Treatment often includes chemotherapy, surgery, and radiation, procedures that are particularly difficult for children. If doctors can turn cancer cells into healthy ones, it would provide patients with an entirely new treatment option – one that could spare them and their families a great deal of pain and suffering.

Rhabdomyosarcoma (RMS) is a devastating and aggressive type of childhood cancer that resembles the muscle cells of children. No one knew if this proposed treatment method, called differentiation therapy, might work in treating RMS. We may still be decades away. But now, thanks to Vacoc’s lab, it looks like a real possibility.

To carry out their mission, Vakoc and his team created a new genetic screening technology. Using genome-editing technology, they were able to track down genes that, when disabled, would force RMS cells to become muscle cells. That’s when a protein called NF-Y appeared. As NF-Y weakened, scientists witnessed an amazing transformation. Vacuk recounts:

“Cells literally turn into muscle. The tumor loses all the qualities of cancer. They go from a cell that just wants to make more of itself into cells that are dedicated to shrinking. Because all of their energy and resources are now devoted to shrinking, they can’t go back into this multiplying state.

This newly discovered relationship between NF-κB and RMS may trigger the chain reaction needed to deliver differential therapy to patients. And the job doesn’t stop at RMS. This technology can be applied to other types of cancer. If so, scientists may one day figure out how to turn other tumors into healthy cells.

“This technology could allow you to take any cancer and look for how to identify it,” explains Vacuk. “This could be a key step toward making differentiation therapy more accessible.”

Previously, Vacock and his team had successfully transformed Ewing’s sarcoma cells into healthy tissue cells. The discoveries of Ewing’s sarcoma and RMS syndrome have been supported by local families who have lost loved ones to these cancers. “They got together and funded us to try to find a new treatment strategy, with some desperation,” says Vacuk.

These families and Vacock’s lab may now be the heroes of a new origin story: a scientific breakthrough that could one day help save children’s lives and revolutionize the treatment of cancer as we know it.

written by: Luis Sandoval, Communication specialist | | 516-367-6826


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National Cancer Institute, Pershing Scone Alliance for Cancer Research, National Institutes of Health, Edward and Martha Geary Fellowship, Miles Levine Impact Award, Christina Rinna Foundation, Mary Rochalski Foundation, Friends of TJ Foundation, Michelle Paternoster Foundation, Summer Road Foundation. , Clark Gillis Foundation, Daniela Conti Foundation, Madi Promise.

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Sroka, M.; et al“Myocyte differentiation reporter screen reveals NF-Y as an activator of PAX3-FOXO1 in rhabdomyosarcoma”, BanasAugust 2023. DOI: 10.1073/pnas.2303859120

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