Back to the future: mechanism-based, mutation-specific combination chemoprevention with a synthetic lethality approach.

There is an increasing recognition that the mutations accompanying carcinogenesis may provide a window of therapeutic advantage designated synthetic lethality, an example of which is reported in this issue of the journal by Huang and colleagues (beginning on page 666). First discovered and studied in yeast, synthetic lethality has basic principles that have encouraged its development for treatment and now prevention in animal models of human cancer, especially malignancies refractory to standard approaches. The pros and cons of this approach and challenges in implementing it clinically are discussed.