homoharringtonine and Rhabdoid-Tumor

Rhabdoid tumors are devastating pediatric cancers in need of improved therapies. We sought to identify small molecules that exhibit. 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 most effective drug to confirm. Small-molecule screening identified the protein-translation inhibitor homoharringtonine (HHT), an FDA-approved treatment for chronic myelogenous leukemia (CML), as the sole drug to which all rhabdoid tumor cell lines were selectively sensitive. Validation studies confirmed the sensitivity of rhabdoid tumor to HHT was comparable with that of CML cell lines. Low expression of the antiapoptotic gene. Rhabdoid tumor cell lines and xenografts are highly sensitive to HHT, at least partially due to their low expression of

Topics: Animals; Apoptosis; bcl-X Protein; Cell Line, Tumor; Cell Proliferation; Drug Resistance, Neoplasm; Female; Gene Expression Regulation, Neoplastic; Homoharringtonine; Humans; Mice; Protein Biosynthesis; Rhabdoid Tumor; Xenograft Model Antitumor Assays