Fig. 2

Strategy for a rational combination-therapy design. The interactions are based on the pathway from Fig. 1. A loss-of-function mutation in gene a is indicated to be a driver mutation for cancer development. The hypothetical case indicates a synthetic-sick interaction between gene a (which is involved in DNA repair) and gene g (which is involved in cellular metabolism). From left to right, inhibition of gene f or gene g in the cancer (a^−/−) background results in synthetic sickness, but not lethality. Synthetic lethality in the cancer background is only achieved by co-inhibition of the genes f and g (or of genes f and h)