The conditional nature of gene essentiality

Essential genes are classically defined as required for cellular viability and reproductive success. Despite this deceptively simple definition, several lines of evidence suggest that gene essentiality is instead a conditional trait. Indeed, gene essentiality has been shown to depend on the environmental and genetic context as well as from the variable ability of cells to acquire adaptive mutations to survive inactivation of seemingly essential genes. Here, we will discuss these findings and highlight the mechanisms underlying the ability of cells to survive an essential gene deletion. Also, since essential genes are prioritized as targets for anticancer therapy, we discuss emergence of bypass resistance mechanisms toward targeted therapies as the result of the conditional nature of gene essentiality. To identify targets associated to a lower risk of relapse (i.e. the return of cancer following remission), we finally call for a coordinated effort to quantify the variable nature of gene essentiality across species, cell types, and growth conditions.