Building high-resolution synthetic lethal networks: a ‘Google map’ of the cancer cell

•Selective killing of cancer cells based on tumor genetics.•RNA interference and clustered, regularly interspaced short palindromic repeats (CRISPR) genome editing can identify contextual vulnerabilities.•Building biological networks to design effective genotype-targeted cancer therapies.

The most commonly used therapies for cancer involve delivering high doses of radiation or toxic chemicals to the patient that also cause substantial damage to normal tissue. To overcome this, researchers have recently resorted to a basic biological concept called ‘synthetic lethality’ (SL) that takes advantage of interactions between gene pairs. The identification of SL interactions is of considerable therapeutic interest because if a particular gene is SL with a tumor-causing mutation, then the targeting that gene carries therapeutic advantages. Mapping these interactions in the context of human cancer cells could hold the key to effective, targeted cancer treatments. In this review, we cover the recent advances that aim to identify these SL interactions using unbiased genetic screens.