Context-dependent synthetic lethality — an emerging precision therapeutic approach

<p>Nature Reviews Cancer, Published online: 23 April 2026; <a href="https://www.nature.com/articles/s41568-026-00929-9">doi:10.1038/s41568-026-00929-9</a></p>In this Review, Chang et al. discuss context-dependent synthetic lethality whereby various genetic contexts produce cancer-intrinsic vulnerabilities and provide a framework that evaluates and considers therapeutic index to enable the translation of synthetic lethality into more selective and durable cancer therapies.