Lineage-Selective Dependencies in Pediatric Cancers
Year: 2024
Type: preprint
Abstract: The quest for effective cancer therapeutics has traditionally centered on targeting mutated or overexpressed oncogenic proteins. However, challenges arise in cancers with low mutational burden or when the mutated oncogene is not conventionally targetable, which are common situations in childhood cancers. This obstacle has sparked large-scale unbiased screens to identify collateral genetic dependencies crucial for cancer cell growth. These screens have revealed promising targets for therapeutic intervention in the form of lineage-selective dependency genes, which may have an expanded therapeutic window compared to pan-lethal dependencies. Many lineage-selective dependencies regulate gene expression and are closely tied to the developmental origins of pediatric tumors. Placing lineage-selective dependencies in a transcriptional network model is helpful for understanding their roles in driving malignant cell behaviors. Here, we discuss the identification of lineage-selective dependencies and how two transcriptional models, core regulatory circuits and gene regulatory networks, can serve as frameworks for understanding their individual and collective actions, particularly in cancers affecting children and young adults.
Authors: K. Elaine Ritter, Adam D. Durbin
Institution: St. Jude Children's Research Hospital
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4399072801