Osteosarcoma (OS) is the most common malignancy of the bone, which arises primarily in children and adolescents, with a second peak in incidence in those over the age of 50. Unfortunately, the survival for patients with metastatic or relapsed osteosarcoma has remained virtually unchanged over the past 30 years, with an overall 5-year survival rate of about 20%. This is mainly due to lack of targetable genetic mutations. This proposal provides compelling evidence that specific RNA modifications may hold great promise for better understanding the mechanism of OS growth and metastasis and therefore, for developing more potent and less toxic therapeutics. Our findings reveal that an enzyme that ...

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Osteosarcoma (OS) is the most common malignancy of the bone, which arises primarily in children and adolescents, with a second peak in incidence in those over the age of 50. Unfortunately, the survival for patients with metastatic or relapsed osteosarcoma has remained virtually unchanged over the past 30 years, with an overall 5-year survival rate of about 20%. This is mainly due to lack of targetable genetic mutations. This proposal provides compelling evidence that specific RNA modifications may hold great promise for better understanding the mechanism of OS growth and metastasis and therefore, for developing more potent and less toxic therapeutics. Our findings reveal that an enzyme that erases methylation mark on the RNA supports OS growth and metastasis. We believe that approaches aimed at silencing the activity of the RNA demethylase will serve as potent therapeutics for treating OS.

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