A new therapeutic option for a particularly aggressive kind of children cancer that originates in muscle tissue may be on the horizon.
Researchers have successfully transformed rhabdomyosarcoma cells into normal, healthy muscle cells. It’s a breakthrough that could lead to the creation of new medications for the brutal disease, as well as other types of human tumors.
“The cells literally turn into muscle,” explains Cold Spring Harbor Laboratory molecular biologist Christopher Vakoc.
“The tumor loses all cancer characteristics.” They’re transitioning from cells that only want to multiply to cells that want to contract. It cannot return to its proliferating condition because all of its energy and resources are now devoted to contraction.”
Cancer is not a single entity. It develops when cells from various regions of the body mutate. Rhabdomyosarcoma is a kind of cancer that primarily affects children and teenagers. It usually begins in the skeletal muscle when cells change, reproduce, and take over the body.
Rhabdomyosarcoma is a fatal cancer with a 50-70 percent chance of survival in the intermediate risk group.
Differentiation therapy is one treatment method that has showed promise. It was discovered when researchers discovered that leukemia cells are not fully mature, similar to undifferentiated stem cells that have not yet fully matured into a specific cell type. Differentiation therapy coerces those cells to continue developing and dividing into particular mature cell types.
Previously, Vakoc and his colleagues successfully reversed the mutation of cancer cells that arise in Ewing sarcoma, another juvenile cancer that typically manifests in the bones.
The researchers sought to investigate if they might replicate their results with rhabdomyosarcoma, which was thought to be decades away from differentiation therapy.
They employed a genetic screening technique to identify genes that could force rhabdomyosarcoma genes to continue developing into muscle cells. They discovered the solution in a protein known as Nuclear transcription factor Y (NF-Y).
Rhabdomyosarcoma cells produce a protein called PAX3-FOXO1, which drives tumour proliferation and is required by the cancer.
The researchers discovered that knocking out NF-Y inactivates PAX3-FOXO1, forcing the cells to continue developing and differentiating into mature muscle cells with no evidence of cancer activity.
According to the researchers, this is a critical step in the development of differentiation therapy for rhabdomyosarcoma and could shorten the timescale for such treatments.
They also claim that their technique, which has now been tested on two different types of sarcoma, could be applicable to additional sarcomas and cancer types since it provides scientists with the tools they need to figure out how to drive cancer cells to differentiate.
“Every successful medicine has its origin story,” Vakoc explains. “And research like this is the soil from which new drugs are born.”
The research has been published in the Proceedings of the National Academy of Sciences.
