Context-dependent genetic interactions in cancer

Genetic co-dependencies have been found in many contexts, from processes during the development of organisms to many diseases in man, including cancer. Genetic interactions - and in particular synthetic lethal phenotypes - have provided fundamental insights into the genetic architecture of cells and identified potential new opportunities for therapeutic interventions. However, recent studies also demonstrated that genetic interactions are highly context dependent and synthetic lethal interactions in one tumor context might not be translatable to others. Therefore, to better define and understand contexts will be a key challenge for future studies to fully exploit genetic interaction networks for target identification and cancer therapy. In this review, we summarize recent developments in mapping context-specific genetic interaction networks with a particular focus on conceptual and experimental advances in the past years. We then discuss genetic and environmental contexts that influence genetic interaction networks. Finally, we outline challenges of putting genetic interaction networks into context and give an outlook on future directions.