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 May 2020, Dr.Durbin has produced data to demonstrate that his target, EP300, is essential for the maintenance of neuroblastoma cell survival. He has also generated preliminary data indicating that his drug, which destroys the target EP300 by directing it toward degradation, reduces the growth of tumor cells in neuroblastoma xenograft models; these data strongly support EP300’s role as a therapeutic target in neuroblastoma and subsequent experiments will reveal the dosing that yields optimal tumor growth inhibition while limiting side-effects

Project Update: As of February 2021, Dr. Durbin has accepted an independent research position, running his own laboratory, as an Assistant Member at St. Jude Children’s Research Hospital, in the Division of Molecular Oncology, Department of Oncology. In this position, he will dedicate 90% of his effort to research pursuits and 10% to the clinical management of children with advanced solid tumors. Treatment of neuroblastoma models with the compound that Dr. Durbin is developing demonstrates no detectable toxicity to organs including lung, heart, brain, muscle, skin, pancreas, colon, small intestine, liver, kidney, bladder, ureter, thyroid, adrenal and gallbladder. Importantly, this drug decreases the target protein that drives neuroblastoma growth and halts neuroblastoma growth. These results suggest that treatment with this novel drug may yield a minimally toxic approach for pediatric cancers that require the same target, including rhabdomyosarcoma, T-ALL, AML and Ewing sarcoma. Dr.Durbin has determined that his therapy is safe, and he’s show that it has the ability to stop neuroblastoma growth in animal models. This is an early indication that this could be a safe and effective therapy for kids. Over the next 6-12 months, Dr. Durbin intends to perform studies to assess combinations of his drug along with the conventional chemotherapies used for the management of neuroblastoma, including retinoic acid with the aim to increase the effectiveness of treatment while keeping toxicity low.

This project was supported by a grant from Genentech.

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