synthetic lethality

High microsatellite instability (microsatellite instability-high, MSI-H) is a genomic phenotype resulting from defective DNA mismatch repair. The continuous accumulation of insertion–deletion mutations generates frameshift neoantigens that increase tumor immune visibility while also producing ...

MTAP loss disrupts the methionine salvage pathway, resulting in the accumulation of 5′-methylthioadenosine (MTA) and partial inhibition of PRMT5 activity. Cancer cells consequently enter a state with limited PRMT5 functional reserve and develop greater dependence on residual PRMT5 activity and ...

In 2016, two independent studies published in Science found that cancer cells deficient in methylthioadenosine phosphorylase (MTAP) were more sensitive to partial depletion of protein arginine methyltransferase 5 (PRMT5).[1,2] This finding emerged from large-scale functional genomic screens and ...