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Therapeutic Targeting of PGBD5-induced DNA Repair Dependency in Pediatric Solid Tumors

Memorial Sloan-Kettering Cancer Center
Alex Kentsis, MD/PhD
Grant Type: 
Reach Grants
Year Awarded: 
Type of Childhood Cancer: 
Solid and Bone Cancers
Project Description: 

While some human cancers occur as a result of age-dependent accumulation of genetic mutations and others are caused by deficiencies in DNA replication or repair, the causes of many oncogenic mutations remain poorly understood. This conundrum is particularly true for solid tumors of children and young adults, as emphasized by their recent genome surveys, revealing a relative paucity of canonical tumorigenic gene mutations. Our current research now implicates the PGBD5 DNA transposase as an oncogenic mutator responsible for site-specific mutations in the majority of childhood solid tumors, including rhabdoid tumors, a lethal childhood cancer. 

Project Goal
This project aims to develop a new therapeutic strategy against PGBD5-expressing childhood solid tumors. Successful completion of this project is expected to lead immediately to clinical trials of improved therapies for the majority of children with refractory solid tumors.