Fig. 2. The principle of synthetic lethality. The concept of synthetic lethality is based on the idea that DNA damage is often repaired by multiple pathways. In this example, pathways A and B are functional in normal cells, while pathway A is impaired in cancer cells. (A) In the absence of an inhibitor for pathway B, cancer cells can survive because the alternative pathway B compensates for the defect in pathway A. (B) When cancer cells are treated with a PARPi for pathway B, both pathways are blocked, leading to cell death. However, normal cells are not affected because the inhibition of pathway B is compensated by the intact pathway A. PARPi: poly(ADP-ribose) polymerase inhibitors. Figure created with BioRender.com.