Fig. 1

Whole-genome CRISPR/Cas9 knockout screens with T-DM1 and DM1 in MDA-MB-453 and MDA-MB-361 cells. A Schematic of whole-genome screens. B Concentration and schedule of T-DM1 and DM1 treatment during the screens. Arrows denote the time at which the screens were terminated. C Cell growth for the control (Ctrl) and drug-treated cultures during the screens (mean ± SEM, n = 3). D Emergence of resistance to T-DM1 and/or DM1 at the end of the screens in cultures that were treated with T-DM1 or DM1 during the screens relative to untreated (naïve) cultures in MDA-MB-453 and E MDA-MB-361 cells (n = 3). Cultures at the end of the screens were treated with DM1 or T-DM1 continuously for 6 days. F HER2 protein expression in control and drug-treated cultures at the end of the screen. β-actin was used as a protein loading control