Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A⁎STAR), 8A Biomedical Grove, Immunos #05, Singapore 138648, Singapore.
Institute of Medical Biology (IMB), Agency for Science, Technology and Research (A⁎STAR), 8A Biomedical Grove, Immunos #05, Singapore 138648, Singapore.
Curr Opin Genet Dev. 2019 Oct;58-59:55-61. doi: 10.1016/j.gde.2019.07.015. Epub 2019 Aug 27.
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 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.
必需基因通常被定义为细胞存活和生殖成功所必需的。尽管这个定义看似简单，但有几条证据表明，基因的必需性实际上是一种条件性状。事实上，已经证明基因的必需性取决于环境和遗传背景，以及细胞获得适应性突变以存活看似必需基因失活的能力的变化。在这里，我们将讨论这些发现，并强调细胞存活必需基因缺失的机制。此外，由于必需基因被优先作为抗癌治疗的靶点，因此我们还讨论了由于基因必需性的条件性质，针对靶向治疗的旁路耐药机制的出现。为了确定与较低复发风险相关的靶点（即缓解后癌症的再次出现），我们最后呼吁协调努力，在不同物种、细胞类型和生长条件下量化基因必需性的变化性质。
