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SCI 17 December 2024 Synthetic lethal strategies for the development of cancer therapeutics (Nature Reviews Clinical Oncology, IF: 81.1) Natalie Y. L. Ngoi, David Gallo, Carlos Torrado, Mirella Nardo, Daniel Durocher & Timothy A. Yap CORRESPONDENCE TO: tyap@mdanderson.org Synthetic lethality is a genetic phenomenon whereby the simultaneous presence of two different genetic alterations impairs cellular viability. Importantly, targeting synthetic lethal interactions offers potential therapeutic strategies for cancers with alterations in pathways that might otherwise be considered undruggable. High-throughput screening methods based on modern CRISPR–Cas9 technologies have emerged and become crucial for identifying novel synthetic lethal interactions with the potential for translation into biologically rational cancer therapeutic strategies as well as associated predictive biomarkers of response capable of guiding patient selection. Spurred by the clinical success of PARP inhibitors in
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