A possible workaround for targeting the untargetable in a childhood nerve tumor
Researchers have identified an indirect way of countering a key genetic lesion in neuroblastoma.
By Tom Ulrich
Credit: Susanna M. Hamilton, Broad Communications
Pediatric cancers tend to have relatively "quiet" genomes compared to tumors in adults. They harbor fewer discrete genetic mutations, especially in genes for readily "druggable" targets (such as protein kinases). Instead, these tumors tend to feature other kinds of genetic alterations, such as duplications or translocations.
Such is often the case in high-risk forms of neuroblastoma, a rare childhood tumor of the nerves. The gene MYCN is frequently amplified (duplicated many times) in these cancers, forcing the tumor cells to overproduce a transcription factor — a kind of protein that helps turn genes on and off and is very difficult to target directly.
In a paper in the Journal of Clinical Investigation, a team led by postdoctoral researcher Liying Chen and Broad institute member and Dana-Farber/Boston Children's Hospital Cancer and Blood Disorders Center pediatric hematologic malignancies co-director Kimberly Stegmaier (both with the Broad Cancer Program) announced the discovery of a potentially druggable weakness in MCYN-amplified neuroblastomas: a survival dependency on EZH2, a MYCN target gene that helps manage many aspects of a cell's identity and behavior.