CRISPR screens identify selective modulation of a pan-essential protein as a therapeutic strategy in MYCN-amplified neuroblastoma

We were interested in whether we could use the primary DepMap dataset, inclusive of the Pediatric Cancer Dependency Map, to identify putative dependencies in MYCN- neuroblastoma which are dispensable in other cancer cell lines. We then used secondary CRISPR screens to identify genes which when deleted are rapidly cytotoxic and validate in vivo, as these targets might have the efficacy of a conventional cytotoxic chemotherapy but with more selectivity. Here we use time course CRISPR and CRISPRi depletion screens, a positive selection cell death screen, and an in vivo screen to identify the nuclear export factor NXT1 as a novel dependency in MYCN-amplified neuroblastoma.