For example, the depletion of 13 targets (i.e., RRM1, TOP2A, TYMS, etc.)in breast cancer cells, 8 targets (i.e., RRM1, TOP1, MTOR, etc.)in glioblastoma cells, and 6 targets (i.e., TYMS, RRM1, TOP1, etc.)in pancreatic cancer cells resulted in a significant loss of cellular fitness, as depicted by the negative fitness effect. Here, TOP2A is linked to familial pancreatic carcinoma.