Synthetic Lethal Interactions in Cancer Therapy.

Silencing of two or more complementary signaling pathways can lead to cell death, while loss of any single genetic function does not show a severe phenotype thanks to backup solutions. This kind of interaction between two or more genes is coined 'synthetic lethality'. Since this was put forward in 1964, vast numbers of synthetic lethal interactions have been defined in yeast, and accumulating evidence suggests that some synthetic lethal interactions occur in humans. Synthetic lethality provides a new way to treat cancer, in which cancer cells can be targeted specifically. One promising candidate is a poly (ADP-ribose) polymerase (PARP) inhibitor, with which clinical trials have been undertaken in patients with germline BRCA1 or BRCA2 gene mutations by leveraging the synthetic lethal interactions between PARP1 and BRCA1 or BRCA2. Here, we review the synthetic lethality interactions exploited in anticancer therapies and the drug resistance that occurs after anticancer treatment using the synthetic lethal strategy.