@article {1469566,
	title = {Small-Molecule and CRISPR Screening Converge to Reveal Receptor Tyrosine Kinase Dependencies in Pediatric Rhabdoid Tumors},
	journal = {Cell Rep},
	volume = {28},
	number = {9},
	year = {2019},
	month = {2019 08 27},
	pages = {2331-2344.e8},
	abstract = {Cancer is often seen as a disease of mutations and chromosomal abnormalities. However, some cancers, including pediatric rhabdoid tumors (RTs), lack recurrent alterations targetable by current drugs and need alternative, informed therapeutic options. To nominate potential targets, we performed a high-throughput small-molecule screen complemented by a genome-scale CRISPR-Cas9 gene-knockout screen in a large number of RT and control cell lines. These approaches converged to reveal several receptor tyrosine kinases (RTKs) as therapeutic targets, with RTK inhibition effective in suppressing RT cell growth in\&nbsp;vitro and against a xenograft model in\&nbsp;vivo. RT cell lines highly express and activate (phosphorylate) different RTKs, creating dependency without mutation or amplification. Downstream of RTK signaling, we identified PTPN11, encoding the pro-growth signaling protein SHP2, as a shared dependency across all RT cell lines. This study demonstrates that large-scale perturbational screening can uncover vulnerabilities in cancers with "quiet" genomes.},
	keywords = {Animals, Antineoplastic Agents, Cell Line, Tumor, CRISPR-Cas Systems, Female, HEK293 Cells, Humans, Mice, Mice, Nude, Mutation, Protein Kinase Inhibitors, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Rhabdoid Tumor, Small Molecule Libraries},
	issn = {2211-1247},
	doi = {10.1016/j.celrep.2019.07.021},
	author = {Oberlick, Elaine M and Rees, Matthew G and Seashore-Ludlow, Brinton and Vazquez, Francisca and Nelson, Geoffrey M and Dharia, Neekesh V and Weir, Barbara A and Tsherniak, Aviad and Ghandi, Mahmoud and Krill-Burger, John M and Meyers, Robin M and Wang, Xiaofeng and Montgomery, Phil and Root, David E and Bieber, Jake M and Radko, Sandi and Cheah, Jaime H and Hon, C Suk-Yee and Shamji, Alykhan F and Clemons, Paul A and Park, Peter J and Dyer, Michael A and Golub, Todd R and Stegmaier, Kimberly and Hahn, William C and Stewart, Elizabeth A and Schreiber, Stuart L and Roberts, Charles W M}
}
