Rhabdoid Tumors Are Sensitive to the Protein-Translation Inhibitor Homoharringtonine.

ABSTRACT:

Purpose

Rhabdoid tumors are devastating pediatric cancers in need of improved therapies. We sought to identify small molecules that exhibit in vitro and in vivo efficacy against preclinical models of rhabdoid tumor.

Experimental design

We screened eight rhabdoid tumor cell lines with 481 small molecules and compared their sensitivity with that of 879 other cancer cell lines. Genome-scale CRISPR-Cas9 inactivation screens in rhabdoid tumors were analyzed to confirm target vulnerabilities. Gene expression and CRISPR-Cas9 data were queried across cell lines and primary rhabdoid tumors to discover biomarkers of small-molecule sensitivity. Molecular correlates were validated by manipulating gene expression. Subcutaneous rhabdoid tumor xenografts were treated with the

SUBMITTER: Howard TP 

PROVIDER: S-EPMC7501142 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature