Validation of a non-oncogene encoded vulnerability to exportin 1 inhibition in pediatric renal tumors.

ABSTRACT:

Background

Malignant rhabdoid tumors (MRTs) and Wilms' tumors (WTs) are rare and aggressive renal tumors of infants and young children comprising ∼5% of all pediatric cancers. MRTs are among the most genomically stable cancers, and although WTs are genomically heterogeneous, both generally lack therapeutically targetable genetic mutations.

Methods

Comparative protein activity analysis of MRTs (n = 68) and WTs (n = 132) across TCGA and TARGET cohorts, using metaVIPER, revealed elevated exportin 1 (XPO1) inferred activity. In vitro studies were performed on a panel of MRT and WT cell lines to evaluate effects on proliferation and cell-cycle progression following treatment with the selective XPO1 inhibitor selinexor. In vivo anti-tumor activity was assessed in patient-derived x

SUBMITTER: Coutinho DF 

PROVIDER: S-EPMC9669237 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature