Researchers at Children’s Hospital of Philadelphia (CHOP) have been awarded a research grant from Alex’s Lemonade Stand Foundation (ALSF), a leading funder of pediatric cancer research, as part of the foundation’s Crazy 8 Initiative, which funds research that will accelerate the development of new treatments and cures for children with cancer. The grant, part of an $18.5 million funding commitment by ALSF, will fund the development of a drug that targets MYCN, a historically “undruggable” transcription factor that drives aggressive pediatric cancers like neuroblastoma and medulloblastoma.
Led by Yael P. Mossé, MD, an attending physician in CHOP’s Cancer Center, the multidisciplinary and multi-institutional group of researchers, which also includes John Maris, MD and Ophir Shalem, PhD from CHOP, will use targeted degradation to promote cancer cell death. Rather than designing a small molecule that inhibits MYCN’s function, the researchers will attempt to identify a MYCN-specific or MYCN complex-specific binder that can be linked to a ubiquitin ligase, which will tag MYCN for destruction and, as a consequence, destroy the tumor.
“One of the holy grails of pediatric cancer drug development is finding a way to directly target MYCN in patient tumors. Our international team is privileged to have the support of the ALSF Crazy 8 Initiative to develop a MYCN-directed drug that we expect will be effective against the most lethal pediatric cancers,” Mossé said. “The Crazy 8 Initiative promotes scientific collaboration among other renowned institutions with a common goal to find cures. On behalf of my project team, I’d like to thank Alex’s Lemonade Stand Foundation for the opportunity to work with my fellow peers to accelerate breakthroughs in pediatric cancer research.”
The collaborative group also includes researchers from MIT, Nurix Therapeutics, St. Jude Children’s Research Hospital, University of California San Francisco, and University of Würzburg.