St. Baldrick’s Grant Awarded to UH Rainbow Physician Researcher for Pediatric Neuroblastoma Study

Dr. John Letterio.

CLEVELAND, Ohio- St. Baldrick's Foundation, the largest volunteer-driven organization funding childhood cancer research, has awarded a $200,000 research grant to John Letterio, MD, Chief of Pediatric Hematology/Oncology at UH Rainbow Babies & Children's Hospital, Director of the Angie Fowler Adolescent & Young Adult Cancer Institute, and Jane and Lee Seidman Chair in Pediatric Cancer Innovation.

The grant will support Dr. Letterio's project titled, "Development of a Novel NF-κB Targeting Agent for Pediatric Neuroblastoma" for the next two years. The research focuses on improving treatment outcomes for children with high-risk neuroblastoma, a cancer known for its high relapse rate despite intensive therapy.

Recent findings suggest the nuclear factor kappa B or NF-κB plays a critical role in the survival of 'persister cells'-cells that evade conventional treatments and drive disease recurrence. Dr. Letterio's research team will study a new class of synthetic compounds-fourth-generation oleanane triterpenoids (SOTs)-designed to inhibit NF-κB activity and reduce tumor-associated macrophages in the tumor microenvironment.

The study includes three elements:

• Aim 1: Define how the dose and duration of exposure to two lead SOTs affects the survival and growth of neuroblastoma cells when grown in cell cultures in the lab.
• Aim 2: Demonstrate the capacity of two lead SOTs to stop the growth of human neuroblastoma tumors grown in mice, in something known as mouse avatar clinical trials.
• Aim 3: Determine the capacity of the two lead SOTs to enhance the response to conventional chemotherapy, drugs commonly used to treat neuroblastoma, and to show that the improved response to chemotherapy is linked to suppression of NF-kB target genes by the drugs under development.

This year also marks the 25th anniversary of St. Baldrick's. UH Rainbow has been a proud supporter, hosting annual head-shaving events for the past 14 years and raising over $1 million for its foundation. Through numerous St. Baldrick's grants, experts at UH Rainbow, UH Seidman Cancer Center, Angie's Institute, and Case Western Reserve University have made significant strides in advancing treatment options for children and young adults diagnosed with cancer.