EW8 shRRM2 and shNT cells were plated in 384-well plates (Greiner Bio-One, 781091) at a density of 2,500 cells/well in the presence of doxycycline. Cells were allowed to attach overnight and then were treated with the FDA-approved oncology drug set (133 compounds; National Cancer Institute, Developmental Therapeutics Program). Each compound was added at a final concentration of 100 nM. Three CHK1 inhibitors and one ATR inhibitor were included in the screen as positive controls. DMSO was used as the negative control. Plates were then incubated at 37° C for 72 hr. Cell viability was quantified using Cell-Titer-Glo luminescence (Promega) and a FLUOstar Omega microplate reader (BMG Labtech) (5 (link),20 (link)). The screen was performed in duplicate and data were analyzed using a normalized growth rate (GR) inhibition approach to account for the effects of the different growth rates of the shRRM2 and shNT cell lines on drug sensitivity metrics (21 (link),22 (link)). GR values were calculated using the online GRcalculator tool (http://www.grcalculator.org/grtutorial/Home.html) (21 (link)).