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Gene discovery could lead to better treatment for childhood cancers

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Li’s 2020 discovery was named one of the biggest biomedical discoveries of the year by the editors of health news site STAT. Li’s latest work builds on this research and suggests that AVIL is even more important than previously thought.

Dysfunctions of AVIL, Li and his team discovered, play a critical role in the development of the two main subtypes of rhabdomyosarcoma. In a scientific paper describing the results, he and his colleagues describe rhabdomyosarcoma as “dependent” on excessive gene activity. They ultimately called AVIL the “authentic oncogene” for rhabdomyosarcoma. “Oncogene” means carcinogen.

AVIL could be the confluence of two different cellular processes that cause soft tissue cells to become cancerous, the researchers note. Blocking AVIL activity, they found, prevented the formation of rhabdomyosarcoma in cell samples from laboratory dishes and in mouse models of the disease.

It’s a promising sign of the discovery’s potential to lead to a new, targeted treatment for rhabdomyosarcoma, a relatively rare but potentially deadly cancer. Even with multimodal therapeutic interventions, the survival rate for high-risk children is less than 20%.

The new research also reveals that AVIL is excessively active in other soft tissue cancers, known as sarcomas. Scientists found that the degree of excessive activity correlated with patient outcomes, suggesting that AVIL may also be a vulnerability for these cancers.

“These findings, together with our previous work in brain tumors, suggest that AVIL is an oncogene that, when overactivated, can trigger the development of several types of cancer,” Li said.

Finding better ways to prevent and treat cancer is an urgent mission for the UVA Cancer Center, which was designated a Comprehensive Cancer Center by the National Cancer Institute this year. The designation recognizes elite cancer centers with the nation’s most outstanding cancer programs. UVA is one of 52 comprehensive cancer centers nationwide and the only one in Virginia.

Li and his team published their findings in the scientific journal PNAS. The team consisted of Zhongqiu Xie, Pawel L. Janczyk, Xinrui Shi, Qiong Wang, Sandeep Singh, Robert Cornelison, Jingjing Xu, James W. Mandell, Frederic G. Barr, and Li.

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