Dr. Adam Durbin, New Young Investigator: Neuroblastoma

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Dr. Adam DurbinDr. Adam Durbin, Young Investigator: Neuroblastoma

Project title: Novel agents targeting EP300-regulated transcription in neuroblastoma

Project Funded: 2019-2021

Neuroblastoma is a pediatric tumor of the peripheral sympathetic nervous system, the nerves that comprise the nervous system outside of the brain and spinal cord. Neuroblastoma impacts nearly 700 children in the US each year. Current therapies for high-risk neuroblastoma contribute to a survival rate of only 50%. Unfortunately, even in those children that survive, treatment-induced long-term toxicities include deafness, cardiac insufficiency, infertility, and increased risk of second cancers.

Adam Durbin, MD, Ph.D. is a CureSearch Young Investigator conducting research at the St. Jude Children’s Research Hospital aiming to develop a new targeted therapy strategy for neuroblastoma. Dr. Durbin identified a protein (EP300) that is necessary for neuroblastoma growth. Upon identification of EP300 as a druggable target, Dr. Durbin worked to develop a novel, bioavailable compound that is able to selectively destroy EP300. During the course of his CureSearch project, Dr. Durbin will investigate this new compound’s ability to stop neuroblastoma growth. If successful, this project will not only offer an innovative treatment strategy for high-risk neuroblastoma, but has the potential to expand into other EP300-dependent pediatric tumors, including myeloid leukemia and rhabdomyosarcoma.

“As both a scientist and pediatric oncologist, I am focused on developing new drugs for children with challenging-to-treat cancers,” said Dr. Durbin. “Funding from CureSearch for Children’s Cancer is critical to the early steps of our work to try to deal with these issues by developing less toxic, more effective therapies for children with cancer.”

Project Update: As of November 2021, Dr. Durbin’s work continues to support his hypothesis that  EP300 is a central controller of neuroblastoma growth and is tractable for therapeutic development. The work presented thus far has begun to identify the mechanism of this function, through regulation of MYCN and histone acetylation, and has provided a tool compound to evaluate the function of EP300 in neuroblastoma. Importantly, mice treated with this compound display no detectable toxicity, though they lose EP300 expression, suggesting that this approach may yield a minimally toxic approach for pediatric cancers that require EP300, which includes rhabdomyosarcoma, T-ALL, AML and Ewing sarcoma.CureSearch thanks Genentech for partnering with us to support this important project. 

This project was supported by a grant from Genentech.

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