摘要
Genetic interactions are functional crosstalk among different genetic loci that lead to phenotypic changes,such as health or viability alterations.A disease or lethal phenotype that results from the combined effects of gene mutations at different loci is termed a synthetic sickness or synthetic lethality,respectively.Studies of genetic interaction have provided insight on the relationships among biochemical processes or pathways.Cancer results from genetic interactions and is a major focus of current studies in genetic interactions.Various basic and translational cancer studies have explored the concept of genetic interactions,including studies of the mechanistic characterization of genes,drug discovery,biomarker identification and the rational design of combination therapies.This review discusses the implications of genetic interactions in the development of personalized cancer therapies,the identification of treatment-responsive genes,the delineation of mechanisms of chemoresistance and the rational design of combined therapeutic strategies to overcome drug resistance.
