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Sending neuroblastoma cells to the trash

Scientists at St. Jude and Dana-Farber Cancer Institute created a compound to selectively degrade the EP300 enzyme that neuroblastoma cells need to survive.

Memphis, Tennessee, November 12, 2021

Dr. Adam Durbin working in a molecular oncology lab wearing white coat and safety gloves

Adam Durbin, MD, PhD, a member of the St. Jude Division of Molecular Oncology, has collaborated with scientists at Dana-Farber Cancer Institute to create a compound that selectively degrades EP300, an enzyme that neuroblastoma cells need to survive.

Cells have a trash system that allows them to degrade, or get rid of, parts they no longer need. This system can be used to degrade enzymes that cancer cells need to survive. This strategy is used in a type of drug compound called a PROTAC. Scientists at St. Jude and Dana-Farber Cancer Institute have made a PROTAC to kill neuroblastoma cells. 

Neuroblastoma is an aggressive childhood cancer that arises from nerve cells. The compound targets an enzyme called EP300. The researchers showed that neuroblastoma needs EP300 to survive. Their EP300-specific PROTAC is called JQAD1. 

“I think of PROTACs like going fishing. On the end of your fishing rod is a hook that attaches to your target, which for us is EP300,” said co-corresponding author Adam Durbin, MD, PhD, Division of Molecular Oncology. “JQAD1 hooks EP300 and reels it into the cell’s normal protein degradation system, basically dragging the enzyme over to the trash. Without EP300, the neuroblastoma cells die.”  

The researchers expanded their study to over 900 cell lines, representing 36 different kinds of cancer. Their findings showed that EP300 alone is important in roughly one third of all human cancers.

Cancer Discovery published a report on this work. 

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