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Treatment with targeted drugs has primarily focused on the genes and pathways that are mutated in cancer, which severely limits the repertoire of drug targets. Synthetic lethality exploits the notion that the presence of a mutation in a cancer gene is often associated with a new vulnerability that can be targeted therapeutically, thus greatly expanding the arsenal of potential drug targets. Here we discuss both the experimental and the computational biology tools that can be used to identify synthetic lethal interactions. We also discuss strategies for using synthetic lethality to discover new drug targets and in the rational design of more potent drug combinations. We review the progress made and future opportunities offered by synthetic lethal approaches to treating cancer more effectively.
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