Deep proteomic and phosphoproteomic profiling of neuroblastoma treated with XPO1 inhibitor Selinexor

ABSTRACT: Neuroblastoma accounts for 15% of cancer-related deaths in children, highlighting an unmet need for novel therapies. Selinexor is a small molecule inhibitor of XPO1 that shuffles cargo proteins with a nuclear export sequence, many of which are essential for cancer growth and cell maintenance, from the nucleus to the cytosol. We systematically tested the effect of selinexor against neuroblastoma cells in vitro and in vivo and used a proteomics screening approach to interrogate unknown mechanisms of action. We found that selinexor induces its cytotoxic effects in neuroblastoma through the nuclear accumulation of p53. By combining selinexor with an aurora kinase inhibitor, alisertib that is already in clinical use for neuroblastoma, we show that p53-mediated lethality can be further augmented supporting clinical testing of this drug combination against neuroblastoma

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): B Cell, Neutrophil, Blood

DISEASE(S): Acute Leukemia,Neuroblastoma

SUBMITTER: Hong Wang  

LAB HEAD: Hong Wang

PROVIDER: PXD026454 | Pride | 2023-03-11

REPOSITORIES: Pride