Converting cancer mutations into therapeutic opportunities

While the use of synthetic lethality has been around for decades in model organism studies, it has only recently been applied to cancer therapy and judging by recent results, with great success. Following on a recent paper that demonstrates the clinical application of this strategy (Fong et al, 2009), Chris Lord and Alan Ashworth further explore the approach and show that poly(ADP-ribose) polymerase (PARP) inhibitors such as Olaparib can selectively target cancer cells defective in phosphatase and tensin homologue (PTEN, Mendes-Pereira et al, 2009) and that methotrexate is selectively lethal to MutS-homologue-2 (MSH2)-deficient tumour cells (Martin et al, 2009).