KRAS and cancer: A genome-wide shRNA library in a pooled format has been applied to identify genes that regulate sensitivity to RAS mutant cancer cells in colorectal DLD-1 cells with and without a mutant form of the oncogene KRAS. A set of mitotic regulators, including ubiquitination, proteasome degradation of mitotic factors, and PLK1, increase the dependency of KRAS-mutant cells on mitotic checkpoints and progression.