Researchers in Virginia have discovered that a gene responsible for the deadliest type of brain tumor is also responsible for a rare, but fatal, childhood cancer. The discovery may open the door to the first targeted treatments for two types of rhabdomyosarcoma, a cancer of the soft tissue that primarily strikes young children and has a survival rate of less than 20%.
Hui Li, PhD, of the University of Virginia School of Medicine’s Department of Pathology and UVA Cancer Center, led a team that discovered in 2020 that the gene AVIL is the oncogene (cancer-causing gene) responsible for glioblastoma, the most lethal form of brain cancer. Less than 7% of patients with glioblastoma survive five years after diagnosis.
In a new study published in the journal PNAS, Li and colleagues detail how malfunctions in AVIL also play an essential role in the development of the two main subtypes of rhabdomyosarcoma. The paper describes rhabdomyosarcoma as “addicted” to the gene’s excess activity and ultimately labels AVIL a “bona fide oncogene” for rhabdomyosarcoma.
“We accumulated multiple lines of evidence supporting [the gene] AVIL is powerful driver for both major types of rhabdomyosarcoma,” Li says. “The tumors are oncogene addicted to AVIL, which supports the rationale to design therapeutic interventions to target AVIL in this childhood cancer.”
AVIL may be the convergence point for two different cellular processes that cause soft-tissue cells to become cancerous, the researchers note. Blocking the activity of AVIL, they found, prevented the formation of rhabdomyosarcoma in both cell samples in lab dishes and in mouse models of the disease.
The new research also reveals that AVIL is excessively active in other cancers of the soft tissue, known as sarcomas. The scientists found that the degree of excess activity correlates with patient outcomes, suggesting that AVIL may be a vulnerability for those cancers as well.
“These findings plus our previous work in brain tumor suggest that AVIL is an oncogene that, when over-activated, may trigger the development of multiple cancer types,” Li says.