FIGURE 1.

siRNA multiplex screen and follow-up deconvolution analysis. A, results from the CPT chemosensitization RNAi screen conducted in MDA-MB-231 breast cancer cells. The y axis represents the normalized activity of each siRNA multiplex in the presence of CPT (EC₅₀) minus the normalized activity of each siRNA multiplex in the absence of CPT. Plate median values were used for normalization. B, deconvolution of the top seven sensitizing multiplexes (designate A–G), with values greater than 2 S.D. from the median, identified RRM1 and RRM2 as gene targets whose silencing significantly enhanced the cytotoxicity of CPT. Targets known to be associated with cellular response to CPT-induced DNA damage were also identified (BRCA1 and ATR) (33).